Condensed Case

A 35-year-old woman needs to have an ovarian cyst removed. She had one delivery that was uneventful. Her mother has a history of bleeding after tooth extraction. The physician needs to determine if there is a bleeding disorder. The coagulation test results are as follows:

PT 12.5 seconds (Reference range, 10.5 to 13.3)

aPTT 32.1 seconds (Reference range, 28.7 to 35.5)

Platelets 320,000/mm3 (Reference range, 150,000 to 400,000/mm3)

Bleeding time 11 minutes (Reference, 8 minutes)

What is the most significant abnormal result in the coagulation panel?

Answer

The bleeding time is the only abnormal test, since it is greater than 8 minutes. This suggests a disorder within primary hemostasis. This can be caused by any disorder of platelets, such as von Willebrand disease, or a problem due to platelet secretion. Or it can be caused by several medications. Tests to rule out von Willebrand disease include factor VIII assay, a vWF antigen and activity, as well as platelet aggregation testing. Upon performing a platelet aggregation, there was only a primary wave for epinephrine, and no response for arachidonic acid. The patient was taking 81 pg of aspirin a day as a preventive measure. This resulted in a prolonged bleeding time. The patient was removed from aspirin and the bleeding returned to normal.

Summary Points

• Hemostasis depends on a system of checks and balances between thrombosis and hemorrhage that involve procoagulants and anticoagulants.

• The systems involved in hemostasis are the vascular system, platelets, coagulation system, and fibrinolytic system.

• Primary hemostasis is composed of platelet function and vasoconstriction.

Secondary hemostasis is composed of fibrin clot formation and fibrin clot lysis.

Platelet aggregation is mediated by von Willebrand's factor (vWF) and platelet glycoprotein Ib (GP1b).

Platelets are small discoid cell fragments that are synthesized in the bone marrow and stimulated by the hormone thrombopoietin.

There are four phases to platelet function at the site of injury: platelet adherence to collagen, platelet aggregation, platelet granule release, and stabilization of the clot.

• Coagulation factors are produced in the liver with the exception of a portion of factor VIII, produced in the endothelial cells.

• The traditional coagulation pathway is divided into the intrinsic, extrinsic, and common pathways.

• The extrinsic pathway is monitored by the pro-thrombin time, while the intrinsic pathway is monitored by the partial thromboplastin time.

• The intrinsic pathway is initiated by factor XII and surface contact with the endothelial cells.

• Tissue factor pathway inhibitor is able to block the activity of the tissue factor: factor VII complex soon after it becomes active.

• Plasma fibrinogen activated by thrombin results in a stable fibrin clot.

• The key components of the fibrinolytic system are plasminogen, plasminogen activators, plasmin, fibrin, fibrin degradation products, and inhibitors of plasminogen and plasmin.

• Streptokinase, urokinase, and tissue plasminogen activator are activators of the plasmin-plasminogen system.

• Tissue plasminogen activator is available as a pharmacological product to break up pathologically formed clots.

• Serine protease inhibitors and the protein C pathway are the major physiologic inhibitors of coagulation.

• The kinin system is activated by factor XII and contributes to vascular permeability.

• The complement system once activated may contribute to the release of procoagulant material.

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