Thrombocytopenia Foods to avoid

Conquer Low Platelets

Alternative And Natural Therapies For Itp (idiopathic Thrombocytopenia Purpura). Live Free From Itp. Complete Program To Increase Platelets. This Is What You Will Learn With this Guide: The Two Herbs That can help bring up your platelets. The Two Vitamins needed to keep those platelets from dropping. What foods may cause your platelets to drop. How science has confirmed the benefits of these herbs in their use with low platelets. Why your doctor may not know about these natural alternatives and how you can assist him in helping you. Different tests that naturopathic doctors do to determine your real state of health that may reverse the course of your body drastically. Understand some of the reasons why people develop low platelets. Discover how your digestive tract may be the culprit to your low platelet level problems. How you can prevent the most drastic step a splenectomy. How you can restore your health so that you dont need any more dangerous drugs. Get your life back and stop ending up in the hospital all the time. Learn why your immune system is attacking your platelets and how to calm it down. Learn what over the counter medications to stay away from if you have low platelets Read more here...

Conquer Low Platelets Summary


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Heparin Induced Thrombocytopenia

A common adverse drug reaction is heparin-induced thrombocytopenia (HIT). The patho-genesis of HIT begins with the formation of antibodies (typically IgG), against platelet factor 4 (PF4), a protein released from platelet granules that binds to and inactivates heparin (55). IgG-heparin-PF4 complexes bind to platelet immunoglobin Fc receptors (FCy Rlla), leading to rapid uptake by splenic macrophages and thrombocytopenia. In addition, FCy Rlla-mediated platelet activation accelerates thrombin generation, contributing to an acquired hypercoaguable state. The risk of developing HIT is dependent upon many variables, including dose and duration of heparin exposure, heparin formulation (unfractionated low molecular weight heparin, bovine porcine), and clinical setting (orthopedic surgery cardiac surgery medical patients) (56). Thrombocytope-nia rarely is severe enough to cause bleeding, but thrombotic complications occur in up to 50 of the HIT patients (57).

Heparininduced thrombocytopenia HIT

Uncommon but sometimes life-threatening condition due to immune complex-mediated thrombocytopenia in patients treated with heparin. Early recognition reduces morbidity and mortality. IgG antibodies formed in response to heparin therapy form immune complexes with heparin and PF4, bind to platelet Fc receptors, trigger aggregation and cause thrombocytopenia. Thrombin activation causes vascular thrombosis and microthrombi cause microvascular occlusion. HIT causes a fall in the platelet count 8d (4 14d) after a patient's first exposure to heparin but may occur within 1-3d in a patient who has recently had prior exposure to heparin. Platelet count generally falls to 60 x 109 L but may fall to

Idiopathic thrombocytopenia and H pylori infection

In 1998, Akiyama and Onozawa 54 demonstrated that a PPI administration was associated with an increase in platelet count in patients with chronic idiopathic thrombocytopenia (ITP). Subsequently, a Lancet paper in a pilot study by Gasbarini et al. 55 described a significant increase in platelet count in 8 of 11 patients with H. pylori, which was successfully eradicated. Since then, there have been numerous case reports and case series reporting that eradication of H. pylori is accompanied by platelet increase in adults patients with ITP. A review by Franchini and Vener 56 i summarized the adult literature. Of a total of 1126 patients with ITP, 64 were infected with H. pylori, eradication occurred in 81 with the platelet response rate occurring in approximately 50 . Subsequently, there has been a randomized control trial looking at the effect of H. pylori eradication in adult patients with chronic ITP involving 36 Japanese patients, 25 of whom were positive for H. pylori 13 of these 25...

Thrombocytopenia in pregnancy

A normal uncomplicated pregnancy is associated with a platelet count in the normal range though up to 10 of normal deliveries may be associ-36 ated with mild thrombocytopenia ( 100 x 109 L). Detection of thrombocytopenia in a pregnant patient requires consideration not only of the diagnoses listed in the previous section but also the conditions associated with pregnancy which cause thrombocytopenia. An additional important consideration is the possible effect on the fetus and its delivery. If thrombocytopenia is detected late in pregnancy, most women will have a platelet count result from the booking visit (at 10-12 weeks) for comparison. Mild thrombocytopenia (100-150 x 109 L) detected for the first time during an uncomplicated pregnancy is not associated with any risk to the fetus nor does it require special obstetric intervention other than hospital delivery. Non-immune thrombocytopenia Thrombocytopenia may develop in association with pregnancy-induced hypertension, pre-eclampsia...

Elevated platelet count

Thrombocytosis is defined as a platelet count 450 x 109 L. May be due to a primary myeloproliferative disorder (MPD) or a secondary reactive 20 feature. If the platelet count is markedly elevated a patient with a myeloproliferative disorder has a risk of haemorrhage (due to the production of dysfunctional platelets), or thrombosis, or both. The patient's history may reveal features of the condition to which the elevated platelet count is secondary. Clinical examination may provide similar clues or reveal the presence of palpable splenomegaly which suggests a myeloproliferative disorder. FBC may provide useful information marked leucocytosis with left shift (in the absence of a history of infection), basophilia or an elevated haematocrit and red cell count are highly suggestive of a myeloproliferative disorder when associated with thrombocytosis. Unusual for reactive thrombocytosis to cause a platelet count 1000 x 109 L. Note platelet counts below this may occur in myeloproliferative...

Heparin Associated Thrombocytopenia

Platelet Factor 4 (PF4) is a heparin binding protein stored in platelets and released into plasma following platelet activation. Heparin PF4 complexes normally do not have adverse sequelae. Specific antibodies to Heparin PF4 complexes generate IgG complexes (Heparin associated Platelet Aggregating Factor) that activate platelets. Platelets are activated by the Fc portion of IgG and Heparin PF4 in the immune complex may bind to adjacent platelets or to the same platelet. These activated platelets release procoagulant microparticles that provide a phos-pholipid surface to accelerate thrombin generation. This leads to platelet activation and thrombosis or their removal by the spleen and thrombocytopenia. thrombocytopenia during heparin therapy ( 50 decrease) absence of other causes of thrombocytopenia resolution of thrombocytopenia after discontinuation of heparin Heparin Associated Thrombocytopenia and Thrombosis (HATT) presents Thrombocytopenia mild seldom 100,000 Onset after heparin...

Immune thrombocytopenia

These conditions are due to IgG and IgM antibodies which react with antigenic sites (usually GPIIb IIIa in ITP, platelet alloantigens in post-transfusion purpura and neonatal isoimmune purpura) on the platelet cell membrane, may fix complement and cause accelerated platelet destruction through phagocytosis by reticuloendothelial cells in liver and spleen. A compensatory increase in bone marrow megakaryocytopoiesis usually occurs which may occasionally prevent or delay the development of severe thrombocytopenia.


Thrombocytopenia is secondary to increased consumption which is likely to occur by adherence to collagen exposed on damaged endothelium. Martin et al. (1990) suggested three categories based on the platelet count class 1 when the platelet count is below 50 10 9 ml, class 2 when it is between 50 and 100*109 ml, and class 3 when it is between 100 and 150*109 ml. Class 1 patients had a higher mean value of lactate dehydrogenase, serum-glutamic oxaloacetic transaminase, serum glutamate-pyruvate transaminase, and indirect bilirubin than class 2 patients and a longer interval between delivery and recovery time. The degree of hypertension was not different between the groups. This classification may aid identification of more severe patients and facilitate earlier aggressive therapy.

Blastic Transformation

Blastic transformation, also called acute blast crisis or terminal phase, occurs in virtually all (nontransplanted) patients with CML, either following an accelerated phase or acutely during the course of stable phase CML.32,65 Most accept the definition of blast crisis as the development of greater than or equal to 30 percent blasts in the marrow or the peripheral blood.89 In the blast crisis stage, progressive anemia and thrombocytopenia occur with death usually due to bleeding or infection. Leukemic involvement of most organs is evident at autopsy. The median survival of those who develop a blast crisis is only about 6 months.

Management Of Coagulopathy

In the massively transfused patients a number of considerations are important which will exacerbate coagulopathy. Packed red cells contain no active platelets. The platelet count should be measured. Banked blood greater than 3 weeks old contains only 10-15 of normal levels of clotting factors V and VIII. Obviously in a brain dead organ donor, spontaneous CNS hemorrhage is significant only insofar as it may further contribute to donor instability. The severely coagulopathic organ donor may, however, become unstable during multiorgan procurement due to excessive blood loss.

Immediate Questions

Is there active bleeding There is increased risk of spontaneous hemorrhage with platelet counts 20,000 mcL. B. Has patient experienced head trauma Intracranial hemorrhage is unusual but can occur with platelet counts 20,000 mcL. C. Is patient febrile Presence of fever increases risk of thrombocytopenia due to significant infection or disseminated intravascular coagulation (DIC). D. Has patient recently received chemotherapy Chemotherapy is a frequent cause of thrombocytopenia. E. Is there a past history of low platelet count This could be consistent with chronic idiopathic thrombocytopenic purpura (ITP) or an inherited thrombocytopenia. F. Does patient take any medication Thrombocytopenia is often seen in patients who take valproic acid.

Acquired Chromosomal Abnormalities

Myeloproliferative Disorders These are disorders that arise at the level of the pluripotent stem cell. Thus, all myeloid lineages are involved, although one predominates. There is overproduction of the three major cell lines in the bone marrow, giving rise to leukocytosis, thrombocytosis, and ery-throcytosis. The MPDs include chronic myelogenous leukemia (CML), essential thrombocytopenia (ET), polycythemia vera (PV) and myelofibrosis with myeloid metaplasia (MF MM). The other myeloproliferative disorders occur in older adults, generally after the age of 40. Essential thrombocytopenia is characterized by a marked increase of platelets in the peripheral circulation and megakaryocytes in the bone marrow. There is an overproduction of erythrocytes in polycythemia vera, and fibrosis of the bone marrow and extramedullary hematopoiesis characterize myelofibrosis with myeloid metaplasia. Fibrosis in the latter can make it difficult to obtain an adequate bone marrow sample. 5.2.2....

Suggested Daily Intravenous Intake of Essential Trace Elements

Can lead to cognitive, perceptual, and motor dysfunction at doses of 200 to 400 mcg d. It can also cause anemia, thrombocytopenia, hemolysis, hepatic dysfunction, and renal failure when given in dosages of 1200 to 2400 mcg d.70 Chromium picolinate might affect dopamine, serotonin, and norepinephrine metabolism in the brain, due to the picolinic acid component.71

Causes of Neutropenia in Children

Very rare exocrine pancreatic insufficiency with neutropenia. Patients present in early childhood with short stature and failure to thrive. Neutropenia may be chronic or cyclic. Patients may also have anemia or thrombocytopenia. 10. Fanconi anemia. Autosomal-recessive inheritance 80 of patients have phenotypic anomalies (including skeletal anomalies of thumb). Initial blood problem is usually thrombocytopenia, not neutropenia.


Many of the pharmacokinetic factors that limit the applicability of diagnosis are not significant during hemoperfusion. Thus, molecular weight, degree of protein, binding in the plasma, and water solubility are not limiting factors during hemop-erfusion because of the high adsorbent area that comes in contact with the blood. The Vd remains important however. Drugs with a large Vd may be completely extracted from the blood as they pass through the adsorbent, but if only a small amount is present in the plasma compartment, only a small total amount may be removed from the body. The most frequent complications are hypotension and thrombocytopenia. Other complications are hypoglycemia, hypocalcemia and hypothermia.

Carmustine Lomustine and Semustine

The nitrosoureas produce severe nausea and vomiting in most patients 4 to 6 hours after administration. The major site of dose-limiting toxicity is the bone marrow leukopenia and thrombocytopenia occur after 4 to 5 weeks. Less frequent side effects include alopecia, stomatitis, and mild abnormalities of liver function. Pulmonary toxicity, manifested by cough, dyspnea, and interstitial fibrosis, is becoming increasingly recognized as a complication of long-term nitrosourea treatment. As alkylating agents, these drugs are potentially muta-genic, teratogenic, and carcinogenic.

Postmarketing Experience 19831986

Reports of other severe untoward events that could have had an immunological basis also appeared in the literature in 1984-1985 thrombocytopenia (Green et at., 1984), hepatitis (Vaz et at., 1984), alveolitis (Hamm et at., 1985) and a systemic lupus erythematosus (SLE)-like reaction (Garcia-Morteo and Maldonado-Cocco, 1983 Schonhofer and Groticke, 1985). Those appearing in the British medical literature could possibly have contributed Haematological Aplastic anaemia Increased bleeding time Leucopenia Thrombocytopenia Positive Coombs' test Haemolytic anaemia

Venous thromboembolism

Low-molecular-weight heparin does not cross the placenta. Limited experience with this agent has been gained during pregnancy, but its use is attractive because its longer half-life allows a once-daily regimen and because it lowers the risk of heparin-induced osteoporosis and thrombocytopenia. Recurrence of pulmonary embolism in adequately anticoagulated patients, any absolute contraindication to anticoagulant therapy, and any serious complication of anticoagulation such as heparin-induced thrombocytopenia are potential indications for transvenous insertion of a permanent inferior vena cava filter in women with venous thromboembolism. These filters have the ability to trap emboli without significantly reducing flow in the inferior vena cava. Recurrence of pulmonary embolism after filter insertion is less than 5 per cent. If possible, anticoagulation should be continued for 3 months after filter insertion to allow lysis of initial thrombosis or any clot trapped by the filter. Apart...

Life Cycle of the Malarial Parasite

Picture Latent Parasites

P. vivax malaria is the most prevalent type of infection and is characterized by periodic acute attacks of chills and fever, profuse sweating, enlarged spleen and liver, anemia, abdominal pain, headaches, and lethargy. Hyperactivity of the reticuloendothelial system and he-molysis are the principal causes of the enlarged spleen and liver these effects often result in anemia, leuko-penia, thrombocytopenia, and hyperbilirubinemia. The cyclical nature of the acute attacks (48 hours for

Chemotherapeutic agents commonly used in MBC

Gemcitabine, a nucleotide analogue that inhibits DNA synthesis has produced an ORR of 20-30 in those with previous exposure to chemotherapy, and 40 as first-line treatment in MBC (40-42). It is well tolerated in general including in the elderly patients. It is associated with a low incidence of nausea, vomiting, and alopecia. The most common dose-limiting toxicities are usually neutropenia and thrombocytopenia. The combination of gemcitabine plus paclitaxel has shown a 68 overall

Early Strategies For Local Delivery

Permanent Persistent Painful Erection

More conventionally, intrathecal delivery via Ommaya reservoirs is used for treatment of leptomeningeal metastases and has resulted in increased survival time and improvement of symptoms. Catheter malposition must be avoided, as it can result in leukencephalopathy in surrounding neurological structures. Other complications include increased intracranial pressure (ICP), infection, and intracranial hemorrhage (15,16). Reservoirs, however, offer significant advantages over multiple lumbar punctures to deliver chemotherapy including improved patient comfort, diminished risk in patients with thrombocytopenia, and a more predictable concentration of drug delivery (16).

Agnogenic Myeloid Metaplasiamyelofibrosis

Agnogenic myeloid metaplasia-myelofibrosis has been described by at least 37 different names, such as idiopathic myelofibrosis with myeloid metaplasia.124,125 Patients with this entity generally present with anemia, massive splenomegaly, and nucleated and tear-drop red cell forms in the peripheral blood. Basophilia and an elevation of the white count with a left shift are not uncommon although as the disease progresses, leukopenia may supervene.126 Early in the disease (before marrow fibrosis occurs) the marrow may be simply hypercellular and the disease unclassifiable. The platelet count may be high, normal, or decreased. Serum B12 and B12 binding proteins tend to be elevated as is the uric acid level, each suggestive of a significant degree of cell turnover.

Platelets Support the Endothelial Barrier

Thrombocytopenia in patients is often characterized by petechial hemorrhages due to capillary leakage. Thrombo-cytopenic animals demonstrate gross purpura and alterations in the microvasculature as evidenced by gaps between endothelial cells and leakage of radioactive tracers into the surrounding tissues. The vascular endothelia are thinner and have open pores and membranous diaphragms. Evidence of a dysfunctional endothelial barrier and tissue edema due to thrombocytopenia have been observed in many experimental models such as the frog hindlimb, the thyroid lobe of

Catastrophic antiphospholipid syndrome

Patients with this rare condition often present critically ill with multiple vascular occlusions death, usually from cardiopulmonary arrest, frequently results ( Asherson, , 1992). There is widespread organ damage with renal dysfunction, hypertension, and respiratory distress with chest radiograph appearances typical of adult respiratory distress syndrome. Thrombotic skin manifestations are common (digital gangrene or ulceration, acrocyanosis, and livido reticularis), as are central nervous system symptoms and signs. Small- and large-vessel thrombosis is a hallmark of the disease, both arterial and venous. There may be a history of systemic lupus erythematosus or primary antiphospholipid syndrome. Laboratory features in addition to the presence of antiphospholipid antibodies include thrombocytopenia, leukocytosis, and an elevated erythrocyte sedimentation rate. Creatinine is often elevated and liver function tests may be abnormal. Treatment must be started early, although it is often...

Contraindications To The Use Of Radiopharmaceuticals For Pain Relief

There are also hematologic contraindications to the use of these radiophar-maceuticals. Significant cytopenias (pretreatment leukocyte count below about 2500-3000 ul, absolute neutrophil count below 1000 ul, platelet count below 60,000-100,000 ul) raise the risks for infection and bleeding. It should be recalled that there are other reasons for pancytopenia in cancer patients, including recent or concurrent chemotherapy or radiotherapy, marrow involvement by tumor, and disseminated intravascular coagulation. Disseminated intravascular coagulation (DIC) is usually subclinical and has been reported in up to 10 to 20 of prostate cancer patients. In this entity, megakaryocyte production and turnover are greatly increased to provide the maximum platelet supply possible, and these platelets have very short half-lives as they participate in the ongoing clotting process. In this disorder, suppression of megakaryocyte production by these beta emitters can lead to precipitous and...

Dosimetry Considerations Y90Ibritumomab Tiuxetan

The use of Y-90-ibritumomab tiuxetan does not require formal dosimetry calculations when used according to FDA-approved guidelines. This approach uses a mCi kg therapeutic dose, but does require In-111 imaging to ensure that an altered biodistribution does not occur. To evaluate for such an altered biodistribution, patients are given trace-labeled In-111-ibritumomab tiuxetan following the rituximab cold infusion. They then undergo serial whole-body gamma camera imaging over several following days to ensure that early postinfusion of the majority of the radioimmunoconjugate remains within the blood pool and over time localizes to target tumor sites. If there is no evidence for an altered biodistribution, patients can then be treated with 0.4 mCi kg of Y-90 up to a maximum of 32 mCi with this approach. Patients with platelet counts between 100,000 and 150,000 should be treated with 0.3 mci kg of Y-90-ibritumomab. radiation dose to patients with normal platelet counts and 65 cGy...

Differential Diagnosis

Henoch-Schonlein purpura (HSP) and hemolytic uremic syndrome (HUS) are common vasculitides in children. HSP typically consists of purpuric rash of buttocks and lower extremities, arthralgias, angioedema, and acute abdominal pain. GI symptoms, including abdominal pain, occult bleeding, massive bleeding, and intussusception, may precede dermatologic findings. Hematuria also can be present. HUS classically presents with a triad of microangiopathic hemolytic anemia, thrombocytopenia, and oliguric renal failure. One of the many complications of HUS is colitis causing melena and possibly perforation. The cause is unknown.

Introduction Of Care Of Oral Cavity

A patient's past medical history directly impacts the medical fitness of a patient for the anticipated extirpative and reconstructive procedure. Adequate cardio-pulmonary function and reserve must be present to tolerate the often prolonged anesthesia time and intravascular fluid shifts associated with many types of reconstructive procedures (11). Such comorbid disease can significantly lower the limits of resectability. Preoperative evaluation and clearance by a hospitalist, cardiologist and or pulmonologist can often help to maximize cardiopulmonary preoperative function. Mental impairment can jeopardize reconstructive success and recovery, as well as limit overall rehabilitative potential. Diabetes, advanced age, vascular disease (i.e., atherosclerosis, hypertension, arteritis), poor nutritional status, hypothyr-oidism, previous radiation therapy, and chronic steroid usage seriously hinders healing and can guide the reconstructive surgeon to either more conservative or more...

Contraindications Cautions and Drug Interactions

Drugs that inhibit platelet function (e.g., aspirin) or produce thrombocytopenia increase the risk of bleeding when heparin is administered. Oral anticoagulants and heparin produce synergistic effects. Many basic drugs precipitate in the presence of the highly acidic heparin (e.g., antihistamines, quinidine, quinine, phenothiazines, tetracycline, gentamicin, neomycin).

Nukhet N Tuzuner and John M Bennett

The acute leukemias are a heterogeneous group of neoplasms affecting uncommitted or partially committed hematopoietic stem cells. The origin of the malignant neoplasm is almost invariably within the marrow. Replacement of the marrow pulp or the repression of normal hematopoietic cells results in variable degrees of anemia, neutropenia, and thrombocytopenia.

Protein and amino acid metabolism

Based on investigations by Mildred and George Burr 194 , it is now recognized that normally a group or family of polyunsaturated fatty acids essential for growth and development cannot be synthesized in humans but instead must be present in the diet 195-197 , and these FFA are defined as essential fatty acids (EFAs). With the introduction of IV nutrition, Collins 198 and Holman 199 described clinical features of EFA deficiency, which occurs in adults and infants after prolonged feeding of a diet deficient in EFA. EFA deficiency occurs not only due to the lack of exogenous supply of EFA from the diet, but also due to elevated plasma insulin levels stimulated by high glucose intakes, which inhibit the release of fatty acids from the adipose tissue stores within the body. Lineolenic, linoleic, and arachidonic acids are recognized precursors of the prostanoid family, important diverse fatty acids involved in cell signal transduction in many immunometabolic functions. Eczematous skin...

Physiology of potassium balance

Hyperkalemia is defined as a plasma potassium level greater than 5.0 mmol l. This may be associated with low, normal, or high total body potassium. True hyperkalemia should be distinguished from pseudohyperkalemia, which may follow in vitro hemolysis and lysis of white blood cells (usually only at levels above 200 * 109 1) or platelets (usually only when the platelet count is above 750 * 10 9 1).

Metabolic Effects of Cytokines in Burns Trauma and Sepsis

Ebb And Flow After Trauma

Both TNF and IL-1 can induce the production of the other 24 and can act synergistically in producing hypotension, thrombocytopenia, metabolic acidosis with increased lactate, anaerobic glycolysis, hyperglycemia, and hypertriglyceridemia 25 . There are beneficial effects of IL-1, however. Taros and colleagues 26 showed in an animal model that administration of IL-1 a lessened the mesenteric ischemia and reperfusion injury and reduced bacterial translocation after burn and sepsis.

Anemia With Hemodynamic Compromise or Complications

With elevated reticulocyte count and no obvious source of blood loss, consider a destructive process. Brisk ongoing hemolysis results in elevation of total and indirect bilirubin and increased LDH without concomitant increase in AST or ALT. Immune-mediated processes are diagnosed using Coombs test. Ill patients with a microangiopathic smear may have hemolytic anemia associated with hemolytic uremic syndrome or thrombotic thrombocytopenic purpura, or disseminated intravascular coagulation (DIC). Low platelets and fibrinogen, elevated PT and PTT, and fibrin degradation products indicate DIC. Inherited disorders (thalassemia, sickle cell anemia, or an enzymopathy) must be ruled out. The possibility of paroxysmal nocturnal hemoglobinuria and Wilson disease should be considered in cases with unclear etiology. VI. Problem Case Diagnosis. Review of systems and past medical, social, dietary, and family history for the 18-month-old boy were benign. Physical exam findings...

Oral Cholecystography Agents

When the OCAs are used for these purposes, they are administered at much lower doses than when used for cholecystography. At the higher doses, the major adverse effects of these compounds are acute renal failure, thrombocytopenia, and athrombocytosis possible minor adverse reactions include diarrhea, nausea, vomiting, and dysuria.

Direct Thrombin Inhibitor Anticoagulants

Two drugs that are direct inhibitors of thrombin but that do not involve antithrombin III or vitamin K in their mechanism of action have been approved to provide intravenous anticoagulation in patients with he-parin-induced thrombocytopenia. Lepirudin (Refludan) and bivalirudin (Angiomax), which are analogues of the leech peptide anticoagulant hirudin, bind in a 1 1 complex with thrombin to inhibit its protease activity. Argatroban (Acova, Novastan), a synthetic analogue of arginine, interacts reversibly with and inhibits throm-bin's catalytic site. Both drugs have a short half-life. Lipuridin is cleared following metabolism and urinary excretion of changed and unchanged drug hepatic metabolism of argatroban is a therapeutic advantage in patients with renal insufficiency. No antagonists for these drugs are available.

Imatinib molecular biology to therapy

Gleevec Clinical Trials

In the Phase II trial in the accelerated phase, patients were required to have 15-30 blasts or more than 30 blasts plus promyelocytes in the peripheral blood or marrow, greater than 20 peripheral basophils, or a platelet count less than 100 x 109 L, unrelated to therapy. With follow-up of up to 3 years, 83 of patients showed some form of hematological response, 40 of patients achieving a CHR. Twenty-eight percent of patients achieved a major cytogenetic response, with 20 complete responses. In this study, significantly improved outcomes for responses and survival were observed for patients treated with 600 mg per day of imatinib compared with patients treated with 400 mg per day. In patients with myeloid blast crisis, the overall response rate to imatinib was 52 , with sustained hematological responses lasting at least 4 weeks in 31 of patients. Nine percent of patients achieved complete remission (fewer than 5 blasts) with peripheral blood recovery and another 4 of patients cleared...

Supplemental Reading

A 23-year old pregnant woman who has been administered IV heparin for treatment of deep vein thrombosis has developed heparin-induced thrombocytopenia. Altering therapy by removing heparin and adding warfarin is not a viable option, because warfarin can cross the placenta and exert an anticoagulant effect in the fetus. Suggest a treatment approach.

Treatment Side Effects

Both Y-90-ibritumomab tiuxetan and I-131-tositumomab have comparable side effect profiles when given at the FDA-approved nonmyeloablative doses. In the series by Dr. Witzig, summarizing the safety of Y-90-ibritumomab tiuxetan in a series of 349 patients treated with this approach, 80 of the patients were noted to have had at least one adverse event. Patients experienced additional toxi-cities such as chills, fever, or flushing 21 , 13 , or 5 of the time, respectively (16). Many of these events were related to the unlabeled rituximab infusion, which is known to cause such reactions. The most important toxicity however is the hematologic toxicity. Unlike traditional chemotherapy, the hematologic nadir of platelets and neutrophils typically occurs six to eight weeks after therapy. In this series of 349 patients, 129 (37 ) experienced grade I or II thrombocytopenia, whereas 63 experienced grade III or IV cytopenia. In addition, 40 of patients experienced grade I or II neutropenia, whereas...

The Bcrabl Rearrangement

Centage both fusion proteins are expressed by alternative splicing events. Comparing the 5' with the 3' M-bcr breakpoint locations, no differences in response to treatment, prognosis, or clinical features exist except for a higher platelet count in patients with the b3a2 transcripts.23

Clinical presentation and outcome

Prominent laboratory findings include leukopenia (especially lymphopenia), thrombocytopenia and elevated liver transaminases (Tab. 3). Most pediatric patients do not manifest hemoconcentration this finding and the prominent respiratory symptoms help distinguish the illness from dengue virus infection in dengue-endemic areas. Renal failure, hyperglycemia and hemophagocytosis have been noted in some patients. Most have abnormal chest radiographs at presentation. Many patients develop complications such as respiratory failure requiring assisted ventilation, ARDS, shock and multiorgan system dysfunction. Severe infections have typically progressed rapidly, with a median duration of symptoms prior to death of 9 days (range 2-31 days). The proximate cause of death is usually respiratory failure. Thrombocytopenia ( )

Prolymphocyte Leukemia

Prolymphocytic leukemia (PLL), once thought to be a variant of CLL,198 is now a well-characterized clinicopathological entity characterized by specific morphological, immunophenotypic, and histological criteria.199,200 The relative frequency of PLL among patients with chronic lymphoproliferative disorders at one large center was 10 percent compared with 80 percent for CLL and 10 percent for hairy cell leukemia.201 B-cell PLL accounts for approximately 80 percent of cases with the more aggressive T-cell PLL accounting for the remainder. PLL is clinically distinct from CLL on the basis of prominent splenomegaly, minimal adenopathy, and extreme leukocytosis with about 50 percent of patients displaying thrombocytopenia, consistent with advanced stage disease (Plate 3-2G,H).

Platelet clumping due to activation during collection

DIFFERENTIAL DIAGNOSIS OF THROMBOCYTOPENIA DURING CHILDHOOD TABLE I-26. DIFFERENTIAL DIAGNOSIS OF THROMBOCYTOPENIA DURING CHILDHOOD AIDS acquired immunodeficiency syndrome HIV human immunodeficiency syndrome HUS hemolytic uremic syndrome ITP idiopathic thrombocytopenic purpura SLE systemic lupus erythematosus TAR thrombocytopenia with absent radii. AIDS acquired immunodeficiency syndrome HIV human immunodeficiency syndrome HUS hemolytic uremic syndrome ITP idiopathic thrombocytopenic purpura SLE systemic lupus erythematosus TAR thrombocytopenia with absent radii. 3. Pseudothrombocytopenia due to EDTA-dependent antibodies, cold agglutinins, or drugs. For ethylenediamine tetra-acetic acid (EDTA)-related problems, recheck platelet counts with alternative anticoagulants (eg, heparin). B. Destructive Thrombocytopenia 1. Immune thrombocytopenia b. Autoimmune diseases with thrombocytopenia as a manifestation. Immune thrombocytopenia associated with cancer, systemic lupus...

Clinical Applications

Molecular genotyping is useful to determine the fetal risk for neonatal alloimmune thrombocytopenic purpura (NATP). In particular, molecular genotyping alleviates the need for platelets when the thrombocytopenia is so severe that it is not possible to obtain sufficient platelets for pheno-typing. 5.2.1 Identification of a Fetus at Risk for Alloimmune Thrombocytopenia

Topoisomerase ITargeting Agents

Topotecan was the first water-soluble CPT analogue approved for clinical use. It has a relatively higher CNS penetration than most other CPTs, due in part to its low plasma protein binding. Schedule-dependent synergism with radiation (concurrent, preradiation, or within 30 minutes after radiation) in vitro has been observed. Renal excretion is the main route of drug elimination. Dosage adjustments are recommended for patients with moderate renal impairment (20-39mL min). Hepatic metabolism by cytochrome P-450 enzymes is minimal. At the standard dose of 1.5 mg m2 day for 5 consecutive days every 3 weeks, noncumulative and reversible neutropenia is the most common dose-limiting toxicity, with grade 4 neutropenia occurring in 81 , febrile neutropenia in 26 , grade 4 thrombocytopenia in 26 , and severe anemia (Hb less than 8g dL) in 40 . Topotecan is approved for use in cisplatin-refractory ovarian cancer, recurrent small cell lung cancer failing frontline chemotherapy, and leukemias.

Preoperative Evaluation of the Patient

We have already emphasized the importance of reviewing any available imaging studies to assess the indication for the biopsy, as well as to select an appropriate guiding technique and plan the route of access and the final target. Equally important, the patient must be screened for systemic conditions and medications that may interfere with the performance of the biopsy. Often, this preoperative contact can be established over the telephone. Any pertinent clinical information relating to past and present diseases is recorded. Patients are questioned about any history of allergic reactions. A list of current medications is also obtained, with special emphasis on anticoagulants and aspirin. If the patient is on aspirin, the biopsy is postponed for six days. In urgent cases, a period of three days may be sufficient to prevent a problem with bleeding. Alternatively, the use of fine needles, or simply the assumption of risk, may be adequate when there is a true medical urgency, and...

Physical Exam Key Points

Petechiae or purpura may be seen with thrombocytopenia in bone marrow failure or infiltration, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, or autoimmune hemolytic anemia. Telangiectasia, palmar erythema, and jaundice may indicate liver disease. Isolated jaundice suggests hemolysis. Lack of pink coloration of palmar creases indicates severe anemia.

Chronic Myelocytic Leukemia

CML is a myeloproliferative disorder in which the crucial pathophysiological event is the fusion of the bcr gene on chromosome 22 and the abl gene on chromosome 9.14 The molecular biological details and cell biological consequences of this rearrangement are discussed in Chapter 20. The diagnosis of CML is confirmed when bone marrow or peripheral blood cells are determined to have a Philadelphia chromosome (i.e., a translocation between the long arm of chromosome 9 and the short arm of chromosome 22) by either molecular or kary-otypic analysis. Although Philadelphia chromosome-negative CML was considered a distinct pathophysiological entity,59 if patients do not evidence such a translocation by any method, they do not have CML. Although the Philadelphia chromosome is considered diagnostic of CML, this translocation has also been noted in patients with disorders clinically consistent with essential thrombocytopenia or other MPDs.61,62 Very rarely patients who present with apparent AML...

Hemodynamic stabilization

Two large-bore intravenous cannulas should be placed to allow fluid access and administration of medication. In a few patients, survival is threatened by the actual volume of blood lost through hemoptysis. Intravenous fluid should be administered commensurate with the vital signs. Routine laboratory analysis should include a hematocrit, platelet count, coagulation profile, arterial blood gases, and renal function studies. Blood should also be typed and cross-matched in case transfusion is required. Any coagulation defects should be corrected. If there is ongoing massive bleeding despite endobronchial management, vasopressors such as intravenous vasopressin (0.2-0.4 units min as a continuous infusion), terlipressin (1-2 mg as a bolus every 6-8 h), or octreotide (50 pg intravenously as a bolus followed by 50 pg h as a continuous infusion) can be used as a temporary measure.

Essential Thrombocythemia

Essential thrombocythemia (ET) is a clonal disorder19 characterized by panmyelosis of the bone marrow with a predominance of megakaryocytes resulting in marked thrombocyto-sis.112-114 Megakaryocyte progenitors may be hypersensitive to thrombopoietin. The platelet count usually exceeds 106 l. Mild leukocytosis (20 to 30,000 l) is often present, but the red cell mass is normal (unless iron deficiency occurs due to bleeding) and must be so to distinguish this entity from polycythemia vera. Bone marrow reticulin may be mildly increased, but an excessive degree of fibrosis excludes ET and suggests the entity of agnogenic myeloid metaplasia with myelofibrosis. Although the bone marrow examination is not diagnostic, clusters of atypical and dysplastic megakaryocytes are generally noted115 (Plate 3-1K). These cells may contain cytoplasmic blebs and may also be observed in the peripheral blood. Large aggregates of platelets including giant and bizarre forms are seen in peripheral blood (Plate...

PDGFB Pericyte Recruitment and Vessel Maturation

Giant Bizzare Platelet

Because of glomerular development irregularities secondary to an absence of mesangial cells, cells that are structurally and functionally related to pericytes. In addition, hematologic abnormalities such as anemia, thrombocytopenia, erythroblastosis, and arteriolar dilation were also present. The other study performed by Betsholtz and group utilized PDGF-B-deficient mice that displayed a similar phenotype and died perinatally as a result of hemorrhage. In 1997, the effects of PDGF-B deficiency were further characterized, indicating that lack of pericytes during vessel growth produces microvascular aneurysms and related these findings to possible pathological complications seen in diabetes mellitus. These studies demonstrated the importance of PDGF-B signal-ing through the PDGF-b receptor in promoting the recruitment of pericytes to developing vessels thereby increasing their stability.

Philadelphia Chromosomenegative

Compared with BCR-ABL-negative CML and CMML, patients with Ph-negative and BCR-ABL-positive CML and Ph-positive CML are younger, have a higher white blood cell count at presentation, a higher incidence of thrombocytosis and peripheral blood and bone marrow basophilia, and a lower incidence of anemia, thrombocytopenia, bone marrow blast percentage, and peripheral blood and bone marrow monocyto-sis.162,168 Patients with BCR-ABL-negative CML respond poorly to therapy and have significantly worse survival rates, with a prognosis that is intermediate between Ph-positive CML and CMML. Only 25 to 50 percent of these patients transform into blastic phase. Most develop an increasing leukemic cell burden, organomegaly, and extramedullary infiltrates, culminating into bone marrow failure and eventually death of the patient.162,163

Box 33 Suggested guidelines for the use of intravenous rTPA in ischaemic stroke108

Exclusion criteria use of oral anticoagulants or INR greater than 1-7 use of heparin in preceding 48 hours or prolonged partial thromboplastin time platelet count less than 100 000 mm3 stroke or serious head injury in the previous three months major surgery within previous 14 days pretreatment systolic BP greater than 185 mmHg or diastolic greater than 110 mmHg rapidly improving neurological condition mild isolated neurological deficits previous intracranial haemorrhage blood glucose greater than 22 mmol L (400 mg dl) or less than 2-8 mmol L (50 mg dl) seizure at stroke onset gastrointestinal or urinary bleeding within previous 21 days or recent myocardial infarction.

Additional evaluation

Additional evaluation may be of aid in the diagnosis of acute uremia. Severe hypocalcemia at the onset of oliguria occurs in rhabdomyolysis and pancreatitis. Very high levels of uric acid accompany tumor lysis, trauma, or muscle damage. Eosinophilia is frequent in acute interstitial nephritis. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are characterized by hemolytic anemia, thrombocytopenia, and the presence of schistocytes, and disseminated intravascular coagulation is characterized by anemia, thrombocytopenia, and prolonged prothrombin, partial thromboplastin, and thrombin times associated with low fibrinogen titers and elevated levels of fibrin degradation products.

Coagulation monitoring Basic coagulation screen

The basic screen consists of a platelet count, prothrombin time, activated partial thromboplastin time and thrombin time. Close attention to blood sampling technique is very important for correct interpretation of coagulation tests. Drawing blood from indwelling catheters should, ideally, be avoided since samples may be diluted or contaminated with heparin. The correct volume of blood must be placed in the sample tube to avoid dilution errors. Laboratory coagulation tests are usually performed on citrated plasma samples taken into glass tubes. Sample tube contains celite, a diatomaceous earth, which activates the contact system thus the ACT predominantly tests the intrinsic pathway. The ACT is prolonged by heparin therapy, thrombocytopenia, hypothermia, haemodilution, fibrinolysis and high dose aprotinin. Normal is 100-140s.

Hematology and oncology

Most cases are mild with platelet counts higher than 100,000 L. All of the other statements are correct. (Rogers, MC, et al. Textbook of Pediatric Intensive Care, 3rd Edition pp. 1406,1407.) 20. D Two forms of acute, heparin-induced thrombocytopenia occur. The mild form occurs in approximately 5 of patients, 4-15 days after initiation of full-dose heparin therapy (platelet counts higher than 100,000 L). Severe thrombocytopenia occurs less frequently. The more severe form is associated with thrombotic complications. All of the other statements are correct. (Gilman, AG, et al. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th Edition pp. 1316.)

Premenstrual Edema and Edema of Pregnancy

Many women retain fluid during pregnancy and during the last days of the menstrual cycle. Breast fullness and subcutaneous swelling or puffiness are the most commonly observed symptoms they are largely the result of elevated circulating hormone levels in the blood. Estrogens possess some mineralocorticoid activity, and thus, when present in relatively high concentrations, may produce some expansion of the extracellular fluid compartment. Excessive premenstrual edema frequently responds well to thiazide therapy. Recent experience has diminished enthusiasm for use of any diuretics in pregnant women. Since the edema of pregnancy is frequently well tolerated, concerns of compromised uteroplacental perfusion, possible ineffectiveness of diuretics in preeclampsia, and the risk of adverse effects of diuretics on the baby (e.g., thiazides can both cross the placental barrier and appear in breast milk, producing electrolyte disturbances and thrombocytopenia in newborns) have led to diminished...

Low MolecularWeight Heparin

Anticoagulant control without laboratory tests. LMWH is more effective than standard heparin in preventing and treating venous thromboembolism. The incidence of thrombocytopenia after administration of LMWH is lower than with standard heparin. Adverse drug reactions like those caused by standard heparin have been seen during therapy with LMWH, and overdose is treated with protamine.

Gaucher Disease Molecular Basis of the Disease

Gaucher disease (GD) is another prevalent autosomal recessive lysosomal storage disorder that is found with higher incidence in the Ashkenazi Jewish population. The carrier frequency is 1 in 18 in this population and 1 in 100 in other populations12 (for comprehensive review on GD, see Reference 13). A defect in the enzyme glucocerebrosidase leads to the accumulation of glucocerebrosides in lysosomal compartments in macrophage monocyte-derived cells, particularly in the liver, bone marrow, spleen, and lung. Several forms of GD exist. Type 1 GD has a wide range of clinical presentations, with some patients being asymptomatic, but can include bone disease, hepatosplenomegaly, anemia, and thrombocytopenia, but without primary central nervous system involvement. Types 2 and 3 have primary central nervous system involvement that varies by age of onset and rate of disease progression. Type 2 GD patients usually have an earlier age of onset than type 3 patients, with acute disease progression...

Activity of carboplatin

Carboplatin can be regarded as a less toxic substitute for cisplatin and is used for similar indications. Patients resistant to cisplatin will also be resistant to carboplatin and vice versa. However, the increased thrombocytopenia seen with carboplatin may be a disadvantage in some combinations, while reduced non-haematological toxicities may be an advantage in others. Further, a low level of non-haematological toxicity makes carboplatin suitable for inclusion in high-dose regimens with bone marrow or stem cell rescue.

Clinical Manifestations

About 25 percent of patients present with fatigue, 25 percent with repeated infections, and 25 percent with splenomegaly, which in a minority of patients may be massive, or with cytope-nias41 (Table 8-1). In 102 newly diagnosed HCL patients, 86 had anemia, 84 thrombocytopenia, and 78 neutropenia.42 Splenomegaly was present in 93 patients. Hepatomegaly is present in 20 percent of patients. Although peripheral adenopathy is rarely found clinically, less than 10 percent of patients have peripheral lymphadenopathy larger than 2 cm now with the frequent use of computed tomographic (CT) scans in the initial evaluation, internal lymphadenopathy is increasingly recognized. Of 43 consecutive patients studied with CT scans, 6 (14 percent) had significant internal adenopathy 3 had massive abdominal adenopathy (larger than 10 cm), and 1 had bulky adenopathy (5 to 10 cm).43 Hairy cell leukemia is typically associated with leukopenia, but up to 20 percent of patients may develop a leukemic phase,44...

Essential 1 thrombocythaemia ET

No association with radiation, drugs, chemicals or viral infection. Not all cases are clonal. Clonal and non-clonal cases may have different natural histories thrombosis is less common in polyclonal 250 ET as is the risk of leukaemic transformation. Platelets in ET are often functionally abnormal showing impaired aggregation in vitro. High platelet counts ( 1000 x 109 L) are associated with an acquired von Willebrand syndrome reduction in the platelet count corrects the abnormality and reduces haemorrhagic episodes.

Highdose chemotherapy HDC with haematopoietic support

The introduction of the haematopoietic growth factors changed high-dose chemotherapy. Administration of these cytokines following bone marrow re-infusion resulted in a dramatic abbreviation of duration of neutropenia. It was also discovered that administration of these factors, either at steady state or following myelosuppressive chemotherapy, resulted in mobilization of haematopoietic progenitors from the bone marrow into the peripheral blood. These 'peripheral blood progenitors' (PBP) could be harvested by leuco-pheresis, then re-infused as haematopoietic rescue following subsequent HDC. PBP autografting is superior to marrow autografting, with shortened neutropenia and thrombocytopenia, and reduced mortality and morbidity.

Treatment of fulminant hepatic failure

The management of fulminant hepatic failure resulting from acetaminophen overdose is based on good intensive care. Optimum management should be directed towards resuscitation and preparation for urgent and safe transfer. Control and protection of the airway is fundamental, particularly as these patients can rapidly become deeply encephalopathic. Sedatives are contraindicated, and patients who cannot be managed safely should be ventilated. Intravenous fluid resuscitation is always necessary and is best directed by either central venous or pulmonary artery pressures. Hypotension may require intravenous vasopressors as well as intravenous fluid. Volume expansion can often correct a mild metabolic acidosis, but bicarbonate infusions should be avoided as the trend in serum bicarbonate is crucial with respect to prognosis (Table2). These patients often experience profound metabolic disturbances, particularly hypoglycemia and hypophosphatemia, which need to be corrected with infusions of 10...

Causes Of Kidney Failure

According to the 1998 USRDS, the annual incidence of pediatric ESRD is 1,087, or 13 per million.1 Many causes of pediatric ESRD are unique (Table 13B.1). Alport's syndrome is the association of nephropathy, deafness, and cataracts. Infantile polycystic kidney disease (ARPKD) is autosomal recessive, occurs one in 10,000 to one in 40,000 live births, and involves both kidneys and liver. Adult or autosomal dominant polycystic kidney disease (AKPDK) occurs one in 250 live births, but only 10 present in the first two decades of life. Hemolytic uremic syndrome (HUS) is a disease of infancy characterized by microangiopathic hemolytic anemia, renal cortical necrosis, renal failure, and thrombocytopenia. IgA nephropa-thy (Berger's disease) presents as a respiratory illness, hematuria, and glomerular mesangial IgA deposits. Henoch Schonlein syndrome (HSP) is characterized by purpuric skin lesions, abdominal pain, arthralgia, and renal dysfunction. Cysti-nosis is a rare, autosomal recessive,...

Clinical Utility of Testing

Currently, the most significant impact of molecular testing on clinical management and genetic counseling is the differentiation of type 2N VWD and mild HA. Both have a mild to moderate reduction in F8 activity, with normal levels of VWF antigen and ristocetin cofactor activity. The autosomal inheritance pattern and the need for use of VWF concentrates rather than pure F8 concentrates make this an important distinction. Differentiation of VWD types 2A and 2B also provides useful information that alters clinical management. Although patients with type 2B VWD are characterized by the presence of variable degrees of thrombocytopenia, the differentiation from type 2A by platelet count is not always possible. The distinction between types 2A and 2B is clinically significant because treatment with vasopressin (DDAVP) is contraindicated in patients with type 2B due to the potential for worsening the thrombocytopenia.

Pregnancy and Fertility

The natural physiological changes in pregnancy, such as hemodilution and a mild thrombocytopenia may help to ameliorate the thrombotic diathesis that is present in patients with PV.123 Pregnancy itself, however, is a physiological hypercoagu-lable state, with an increase in procoagulant clotting factors (e.g. factor VII, factor VIII, and fibrinogen) and a decrease in natural anticoagulants (e.g., free protein S), occurring from about the third month of pregnancy.124

Thromboprophylaxis for the ICU patient

Critically ill patients frequently have several coexistent risk factors for thromboembolic disease, in particular prolonged immobility, surgery, and indwelling vascular access catheters. Therefore they may benefit from thromboprophylaxis. However, they may also be at increased risk of hemorrhage due to recent surgery, hemostatic dysfunction secondary to renal failure (which also reduces heparin clearance), severe hepatic disease, or thrombocytopenia. These factors are relative contraindications to anticoagulation. As these patients form a highly heterogeneous group, the risk-benefit ratio will vary from patient to patient. There is a paucity of data on the risks and benefits of thromboprophylaxis or anticoagulant regimens in this group of patients.

Class Ia drugs quinidine procainamide disopyramide

Quinidine used to be popular as an effective antiarrhythmic agent against both supraventricular and ventricular arrhythmias, but has fallen into disuse after a large meta-analysis suggested excess mortality due to drug-induced torsade de pointes. Quinidine directly suppresses sinus node and atrioventricular node conduction and increases the refractory period of atrial, ventricular, and His-Purkinje tissue, although an anticholinergic action may increase atrioventricular nodal conduction. The most important side-effect is torsade de pointes associated with QT prolongation. Other side-effects are seen in the gastrointestinal system, together with tinnitus, thrombocytopenia, and hypotension. The drug may precipitate digoxin toxicity. The drug is metabolized hepatically and dose reduction is necessary in patients with hepatic disease.

Management of venous thromboembolism in the ICU

Heparin acts by binding to and potentiating the action of antithrombin, which inhibits activated factor X and the action of thrombin. A standard regimen is an initial 5000-IU intravenous bolus of unfractionated heparin followed by a continuous intravenous infusion of 25 000 to 35 000 units over 24 h to ensure rapid achievement of full therapeutic anticoagulation. The activated partial thromboplastin time is measured at 4 h, aiming to maintain a ratio of 1.5 to 2.5. Dosage adjustments are followed by monitoring activated partial thromboplastin time every 4 h until stable anticoagulation is achieved, and then every 12 to 24 h. Omission of the bolus dose and reduction of the initial infusion rate, with the aim of maintaining the activated partial thromboplastin time ratio at 1.5, is advisable in patients with platelet counts of less than 50 * 109 l, within 24 h of surgery, or with a recent cerebrovascular event or gastrointestinal bleed. Bleeding associated with heparin...

Microvascular thrombosis

Microvascular thrombosis is a characteristic of a variety of conditions ( ,.3) including DIC, thrombotic thrombocytopenic purpura, and the purpura ulminans syndrome. These conditions may also be associated with large-vessel thrombotic manifestations, both arterial and venous. In DIC clinical attention is often directed towards the bleeding manifestations microvasular thrombosis causing endorgan damage may go unrecognized unless it is overt. The microangiopathic process in thrombotic thrombocytopenic purpura causes widespread small-vessel platelet thrombi with neurological, renal, and other endorgan damage, as well as hemolysis, red cell fragmentation, and thrombocytopenia. Thrombotic thrombocytopenic purpura differs from the hemolytic uremic syndrome in which the microvascular thrombosis is restricted to the kidney. The pathogenesis of thrombotic thrombocytopenic purpura is unknown, but both high-molecular-weight multimers of von Willebrand factor and calpain, a...

Management of PV in Pregnancy

To decrease the thrombohemorrhagic complications the Hct should be maintained below 0.45, by phlebotomy if possible. Close monitoring of the Hct and platelet count should be performed on a monthly basis. Low-dose aspirin (75 mg) appears For patients with previous fetal loss or those at high risk of thrombosis, low-molecular weight heparin has been reported to be useful in patients with ET.135 Anticoagulation should be continued for 6 weeks postpartum and it is important to watch for rebound increases in the Hct and platelet count in this period.

Complications of massive transfusion

Hemostasis may already be abnormal due to the underlying condition. During massive transfusion of red cells, platelet numbers fall as few functioning platelets exist in whole blood that has been stored for more than 48 h. Factors V and VIII are reduced after storage for a few days, and remaining levels may be diluted if large volumes of intravenous crystalloid or colloid are given. In addition, DIC may be provoked by release of thromboplastin-like material from platelets, white cells, and red cells broken down during storage of red cells and because of partial activation of coagulation factors. The extent of hemostatic derangement varies widely and is not predictable according to the volume of red cells transfused. Therefore prophylactic replacement formulas (e.g. platelets and fresh frozen plasma after every eight units of red cells) are not recommended. It is preferable to monitor hemostasis and use fresh frozen plasma when abnormalities of the coagulation system exist....

Acute Management of Essential Thrombocythemia

Patients presenting with ET-related hemorrhage may paradoxically need platelet transfusion to increase the number of normally functioning platelets. Platelet apheresis to reduce the platelet count rapidly while the response to hydroxyurea is awaited has sometimes been used for both persisting hemorrhage and evolving thrombosis. Early use of aspirin (300 mg) in ischemic or thrombotic situations is recommended, and anticoagulation with heparin or warfarin can be considered. Some

Chronic lymphocytic leukemiassmall cell lymphoma

Chronic lymphocytic leukemia is a low-grade lymphoma marked by a peripheral lymphocytosis of CD5+, CD20+, CD23+ small lymphocytes that are similar in morphology to normal lymphocytes. BCL-2, which is expressed at low levels in normal lymphocytes, is expressed at high levels in more than 70 of CLL cases but this is rarely, if ever, due to a t(14 18). Staging based on presence of lymphadenopa-thy, organomegaly anemia or thrombocytopenia can provide prognostic information, those in the best prognostic groups enjoying normal mean survival times.

Affecting T cells B cells and neutrophils

An rare autosomal recessive or sometimes X-linked disorder where T 408 cells, B cells and granulocytes are absent. Such children present with serious infection at birth or shortly afterwards. They have no lymph nodes or tonsils, and the usual thymic shadow is absent. Bone marrow is hypoplastic, and there may also be thrombocytopenia and anaemia. It appears to be a pluripotential stem cell failure and carries a dire prognosis. The only curative therapy is BMT.

Chapter References

Barton, J.R., Riely, C.A., Adamec, T.A., Shanklin, D.R., Khoury, A.D., and Sibai, B.M. (1992). Hepatic histopathologic condition does not correlate with laboratory abnormalities in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet count). American Journal of Obstetrics and Gynecology, 167, 1538-43. Martin, J.N., Blake, P.G., Lowry, S.L., Perry, K.G., Files, J.C., and Morrison, J.C. (1990). Pregnancy complicated by preeclampsia-eclampsia with the syndrome of hemolysis, elevated liver enzymes, and low platelet count how rapid is postpartum recovery Obstetrics and Gynecology, 76, 737-41. Sibai, B.M., Taslimi, M.M., El-Nazer, A., Amon, E., Mabie, B.C., and Ryan, G.M. (1986). Maternal-perinatal outcome associated with the syndrome of hemolysis, elevated liver enzymes, and low platelets in severe preeclampsia-eclampsia. American Journal of Obstetrics and Gynecology, 155, 501-9. Weinstein, L. (1982). Syndrome of hemolysis, elevated liver enzymes, and low platelet count a...

Maternal and fetal outcome

The most feared, but fortunately rare, complications of HELLP are liver subcapsular hematoma and rupture with shock. Other maternal complications include aggravation of thrombocytopenia with coagulation disorders or disseminated intravascular coagulation (DIC). Depending on definition, DIC occurs in up to 21 per cent of cases, but seems mainly related to the presence of abruptio placentae which represents the second most common complication (Table,1). Acute renal failure, congestive heart failure, and pulmonary edema are frequent and occur more often with postpartum onset. Severe ascites occurs in up to 10 per cent and correlates

Melphalan Combined with Buthionine Sulfoximine

Able patients, there were 7 partial responses (PR), 2 minor responses (MR), 9 stable disease (SD), and 13 patients with progressive disease (PD). Nearly all patients experienced grade-3 leukopenia and thrombocytopenia, plus grade-2 nausea. There were two toxic deaths on study secondary to renal and CNS toxicity. At autopsy, both children had evidence of mid-brain edema and eosinophilic necrosis of the pons. Other patients on study showed no consistent pattern of impending renal neurologic toxicity (Anderson et al. 1998). A phase-I study of BSO with melphalan is underway in the New Approaches to Neuroblastoma Therapy (NANT) consortium (N9902), which increases the melphalan to myeloablative doses with peripheral blood stem-cell support,while holding the BSO infusion constant, with close monitoring for possible renal or neurologic toxicity.

Stage 1 primary infection

Entry of HIV-1 or HIV-2 through a mucosal surface after sexual contact, direct inoculation into the bloodstream by contaminated blood products, or IV drug abuse can be followed by a transient febrile illness up to 6 weeks later associated with oral ulceration, pharyngitis, and lym-phadenopathy. Photophobia, meningism, myalgia, prostration, encephalopathy and meningitis may also occur. FBC may show lym-phopenia or lymphocytosis often with atypical lymphocytes, neutropenia, thrombocytopenia or pancytopenia. Major differential diagnoses are acute viral meningitis and infectious mononucleosis. False +ve IM serology may occur. Specific IgM then IgG antibody to HIV appears 4-12 weeks after infection and routine tests for HIV may be -ve for up to 3 months. However, the virus is detectable in plasma and CSF from infected individuals during this period and the patient is highly infectious.

Extragastric manifestations of H pylori infection in children

With the increasing awareness among clinicians of H. pylori infection over the last decade, there have been a number of reports on the consequences of adverse effects from H. pylori infections outside the gastrointestinal tract (Tab. 1). Studies purporting the association between these manifestations of H. pylori infections are weak in terms of design and are not reviewed in this chapter. However, there are two manifestations that need to be mentioned the first is refractory iron-deficiency anemia and the second is idiopathic thrombocytopenia (ITP) 45 .

Proposal for a sixgroup translocation cyclin D classification of multiple myeloma tumors

In addition to tumor mass and secondary features, which represent a host response to MM (anemia, thrombocytopenia, bone disease, immunodeficiency, etc.), the intrinsic properties of the tumor cell are also informative in predicting the prognosis and the response to existing therapies. For example, it has been well documented that an unfavorable outcome is

Clinical features

Hepatosplenic T-cell lymphomas present with hepatosplenomegaly, usually without peripheral lymphadenopathy and without lymphocytosis. There is almost always thrombocytopenia and most patients are anaemic. Liver function tests are usually abnormal with moderate elevation of levels of transaminases and alkaline phos-phatase. Serum lactate dehydrogenase level may be very high 334 .

Adverse Effects and Drug Interactions

The sulfonamides do cause hypersensitivity reactions (e.g., rashes, eosinophilia, and drug fever) in a small number of patients. Other rare allergic reactions include vasculitis, photosensitivity, agranulocytosis, and thrombocytopenia. Stevens-Johnson syndrome is also associated with sulfonamide use it is characterized by fever, malaise, erythema multiforme, and ulceration of the mucous membranes of the mouth and genitalia. Hemolytic anemia may develop in persons with a genetic deficiency of red blood cell glucose-6-phosphate dehydrogenase (G6PD).

Assessment of individual organ failure

Hematological function coagulation abnormalities are probably the most important indicator of hematological malfunction and are best measured by the platelet count, the prothrombin time, and the activated partial thromboplastin time. A low hematocrit or an abnormal white cell count may be included.


131I-Metaiodobenzylguanidine (MIBG) is a guanethi-dine derivative that is structurally similar to norepi-nephrine, and therefore concentrates in the neurose-cretory granules of catecholamine-secreting cells. Radiolabeled MIBG provides very sensitive and specific visualization of primary and metastatic neuroblastoma by scintigraphy (Shulkin and Shapiro 1998). In an attempt to deliver higher doses of tumor-specific radiotherapy and avoid normal organ toxicity, iodine-131 MIBG therapy has been used in pilot trials since the mid 1980s, with more than 500 children reported in the literature. Initially, it was shown to induce 30-40 response rate in highly refractory relapsed patients, without significant non-hematologic toxicity (Klingebiel et al. 1991 Matthay et al. 1998 Voute et al. 1991). At low and moderate doses, up to 12 mCi kg of 131I-MIBG, the main toxicity has been thrombocytopenia, usually self-limited. Phase-I dose escalation studies showed that higher doses, up to 18 mCi kg,...

Clinical Presentation

Cytomegalovirus disease is found most commonly one to four months after transplantation. Manifestations of CMV range from asymptomatic viremia to lethal disseminated disease. Mild to moderate disease presents with fever, malaise, headache, arthralgias and myalgias. Laboratory abnormalities include leucopenia and thrombocytopenia. End organ involvement usually correlates with the type of transplant, thus, hepatitis occurs in liver recipients, glomerulopathy in renal transplants, pancreatitis in pancreatic transplants, and pneumonitis in lung and heart-lung recipients. Other organs that can be affected are the gut (gastritis, esoph-agitis, colitis), central nervous system (encephalitis, polyradiculopathy), and retina (retinitis). Colitis usually presents with diarrhea that is occasionally bloody, and it may be complicated by the formation of ulcers and perforation. Retinitis is significantly less common in transplant recipients than in patients with HIV infection.

Principles of management

Examine for signs of (i) infection (e.g. pyrexia, purulent sputum, catheter sites, neutrophilia, falling platelet count, CXR, meningism), (ii) cardiovascular instability (hypotension, increasing metabolic acidosis, oliguria, arrhythmias), (iii) covert pain, particularly abdominal and lower limbs (e.g. compartment syndrome, DVT), (iv) focal neurological signs (e.g. meningism, unequal pupils, hemiparesis), (v) respiratory failure (arterial blood gases), (vi) metabolic derangement (biochemical screen). If any of the above are found, treat as appropriate. Psychosis should not be assumed until treatable causes are excluded.

Infection in immunocompromised hosts AIDS patients

Infection with T. gondii in these patients can involve the brain, the lung, and the eye. A multiorgan involvement with acute respiratory failure and haemodynamic abnormalities, as in septic shock, have been described (Lucet et al. 1993 Al-Kassab et al. 1995). The association of high fever, acute dyspnea, recent onset of thrombocytopenia, and a very high level of lactate dehydrogenase activity are suggestive of disseminated toxoplasmosis.

Hemostasis and rheology

The prothrombin and activated partial thrombin times should normalize by the third postoperative day if the graft is working. Preoperative thrombocytopenia does not always respond to platelet transfusion and usually takes longer (up to a week or more) to recover. Hemoglobin concentration should not exceed 10 g dl to avoid increasing blood viscosity and the risk of portal or hepatic arterial occlusion. Clotting factors should not be given routinely because the prothrombin time is a valuable guide to graft function. In the presence of continued blood loss, thromboelastography should be used to determine the cause. Aprotinin should be continued if there is evidence of continuing fibrinolysis and cryoprecipitate given if fibrinogen levels are low. Reasonable clotting indices suggest a surgical cause and should prompt re-exploration intra-abdominal clot may cause the abdominal compartment syndrome, clotting factor consumption, clot expansion, and hyperbilirubinemia.

Adverse Effects Contraindications and Drug Interactions

Myelosuppression is the most common serious adverse effect of ganciclovir treatment therefore, patients' blood counts should be closely monitored. Neutropenia and anemia have been reported in 25 to 30 of patients, and thrombocytopenia has been seen in 5 to 10 . Elevated serum creatinine may occur following ganciclovir treatment, and dosage adjustment is required for patients with renal impairment. In animal studies, ganciclovir causes decreased sperm production, teratogenesis, and tumor formation.

Laboratory and Radiologic Studies

The reconstructive surgeon should review the laboratory and radiologic exams ordered by the extirpative surgeon during the preoperative and metastatic workup of the head and neck patient. Abnormal liver function, platelet count, blood urea nitrogen, prothrombin, and or prothromboplastin time may lead to significant intraoperative blood loss and post-operative hematomas and possible compressive flap loss and or infection. These abnormalities need to be investigated and corrected as much as possible preoperatively. Preoperative albumin, prealbumin, and leukocyte count can give an estimate of the level of malnourishment that can affect post-operative healing. Usually computed tomography (CT) and magnetic resonance imaging (MRI) scans of the head and neck region are the dominant radiographic studies ordered. These studies complement and confirm the history, physical exam, and endoscopic evaluation, and help to further delineate the tumor extent locally, regionally, and distantly. This is...

Epidemiology and clinical features of avian influenza in children

Similar to the Thailand cases, the most common laboratory abnormalities noted were lymphopenia, thrombocytopenia and elevated transaminases. All had extensive consolidations on chest radiographs, which progressed despite aggressive therapy. All developed respiratory failure requiring mechanical ventilation, and 7 8 children died, despite aggressive supportive care and treatment with oseltamivir, ribavirin and or steroids for ARDS. Two other children were identified with probable or confirmed H5N1 infection during the same outbreak 44 . A 9-year-old girl presented with fever, watery diarrhea, shock and lethargy. Initial laboratory tests including cerebrospinal fluid were normal. She had fulminant shock, became comatose and died within 24 hours. No influenza tests were performed. However, 8 days later, her 4-year-old brother presented with fever, headache, vomiting and profound watery diarrhea. His initial laboratory values were remarkable only for...

Platelet refractoriness

Occasionally patients show little no increment in the platelet count after platelet transfusions. This is called platelet refractoriness. May be due to physical or immunological mechanisms in the patient. The commonest physical mechanism is of platelet circulatory half-life reduction caused by concurrent sepsis or coagulopathy e.g. DIC. Immunological causes include induction of anti-HLA antibodies due to allosensitisation from previous transfusions or generation of anti-platelet antibodies such as in ITP. Investigation should be considered if platelet transfusions fail to maintain a platelet count 10 x 109 L at all times.

Morphologic Subtypes Refractory Anemia RA

Anemia is the main manifestation (hemoglobin below 11 g dl with a low reticulocyte count) with variable dyserythropoiesis alone or accompanied by DysG and DysM (Table 14-7). However, the first hematological manifestation could be thrombocy-topenia alone or more rarely neutropenia alone. Therefore, this type might be more appropriately termed refractory cytopenias (RC). Granulocytopenia or thrombocytopenia or both may be minimal or absent. Blast cells are not present in the peripheral blood (less than 1 percent) and less than 5 percent in the bone marrow. Ringed sideroblasts should be less than 15 percent. The WHO committee11 has proposed to separate refractory cytopenia patients into two categories RC with minimal dysplasia and RC with the multilineage dysplasia, a distinct subset with an unfavorable outcome.

Assessment of disorders of coagulation in critical care medicine

General screening should include at least a platelet count, prothrombin time, and activated partial thromboplastin time. The outcome of these tests may help to establish the cause of bleeding (Table 1). It should be stressed that severe profuse bleeding may be the first sign of overt DIC ( T bl ,.2).

Loop Or Highceiling Diuretics

Loop or high-ceiling diuretics causes a vasodilatory effect and increase renal blood flow before diuresis. The most common side effects are fluid and electrolyte imbalances such as hypokalemia, hyponatremia, hypocalcemia, hypomag-nesemia, and hypochloremia. Hypochloremic metabolic alkalosis may result. Orthostatic hypotension can also occur. Thrombocytopenia, skin disturbances, and transient deafness are seen rarely. Prolonged use can cause thiamine deficiency.

Red cell transfusions in cancer patients

A low haemoglobin in a patient with cancer is also common and requires careful diagnostic evaluation. Elimination of obvious causes such as bleeding from a gastrointestinal malignancy are important before repeated red cell transfusions are given. A one-unit blood transfusion should raise the haemoglobin by approximately 1 g dl. Transfusion may reduce the platelet count, so platelet transfusion may be required before or after blood transfusion.

Pretransplant Treatment

In deciding which patients are fit enough to receive dental care prior to transplantation, the dentist and physician should consult together about the proposed treatment and its risks vs. benefits to the patient. Issues to be discussed include the ability of the patient to tolerate the planned procedures, the need for additional pretreatment screening tests if surgical treatment is indicated e.g., bleeding time, prothrombin time, partial thromboplastin time and platelet count. If significant abnormalities are found in the bleeding or coagulation profiles, the need to use antifibrinolytic agents, fresh frozen plasma or platelet replacement should be discussed.

Indications for platelet transfusion

Thrombocytopenia d. immune thrombocytopenia (only in severe bleeding). Platelet transfusions are contraindicated in thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, and heparin-induced thrombocytopenia because the underlying tendency is for thrombosis rather than bleeding.

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