a. Prolonged whenever plasma levels of one or more of the factors in the extrinsic pathway (V, VII, X, prothrombin, or fibrinogen) fall to levels below ~30% of normal. PT measures thrombin generation following activation of factor X by factor VIIa.
b. PT can be expressed as an international normalized ratio (INR), calculated as patient PT/control PT to the power of the international sensitivity index (ISI). The ISI is a measure of the sensitivity of each individual laboratory's thrombo-plastin reagent to coagulation factor deficiencies. The INR allows for uniform monitoring of the degree of anticoagulation in different laboratories.
c. PT is prolonged at birth. Causes of prolonged PT include vitamin K deficiency, DIC, liver disease, congenital factor deficiencies, and oral anticoagulant therapy.
4. APTT. Becomes prolonged whenever plasma levels of one or more coagulation factors other than factor VII drop below ~30% of normal. Reflects plasma concentration of the four contact factors (XI, XII, prekallikrein, and high-molecular-weight kininogen [HMWK]) and factors II, V, VIII, IX, and X. APTT is prolonged in healthy newborns and reaches adult values by ~6 months of age. The most common cause of prolonged APTT is heparin contamination in samples obtained from indwelling catheters. Other causes of prolonged APTT are congenital factor deficiencies, DIC, liver disease, and lupus anticoagulant.
5. Thrombin time. Measures conversion of fibrinogen to fibrin. It is prolonged by heparin, hypofibrinogenemia, and dysfibrino-genemias.
6. Platelet aggregation testing. Requires platelet count > 100,000/mm3 and relatively large volume of blood (> 10 mL). Patterns of aggregation to ADP, epinephrine (EPI), collagen, arachidonic acid, and ristocetin are measured. Patients with vWD show decreased aggregation with ristocetin as do those with Bernard-Soulier syndrome. In platelet storage pool disease, abnormal aggregation to ADP, EPI, and collagen is seen. Patients with Glanzmann thrombasthenia show abnormal aggregation to ADP, EPI, collagen, and arachidonic acid.
7. Plasma fibrinogen concentrations. Decreased in patients with significant DIC.
8. Fibrin split products and D-dimer. Increased levels are consistent with DIC.
9. Bone marrow aspiration and biopsy. Indicated in bleeding patients when malignancy or aplasia is suspected.
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