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INTRODUCTION

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Hemostasis relies on an intact coagulation cascade for adequate clotting. Any disruption or deficiencies in the cascade can lead to severe and devastating clinical complications. The classic plasma-mediated hemostasis has been depicted as two independent pathways—the intrinsic and extrinsic pathways. Together, they will lead into a common pathway to generate thrombin and ultimately fibrin monomers for clotting.

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Tissue factor-initiated coagulation has three phases: initiation phase, amplification phase, and a propagation phase. The extrinsic pathway is recognized as the initiating phase to generate small amount of thrombin through the release of tissue factor. The amplification and propagation phase is due to the small amount of generated thrombin from the extrinsic pathway to activate important factors of the intrinsic pathway to increase thrombin production. Ultimately, the byproduct of these two pathways leads to the activation of fibrinogen to produce hemostasis.

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CONGENITAL FACTOR DEFICIENCIES

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Factor VIII Deficiency

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The most common hereditary deficiency is hemophilia A (factor VIII deficiency) with a frequency of 1:10,000 births. The occurrence is higher for this particular blood disorder because of the X-linked recessive inheritance nature. Males are generally more affected than females. Most commonly, patient may present with hematuria, hemarthroses, or spontaneous hemorrhage. The severity of hemophilia A depends on the level of factor VIII represented by the type of mutation. Levels as low as 1%–5% of normal are adequate to reduce the severity of spontaneous bleeding in joints, muscles and vital organs.

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In the case of a major surgical procedure, factor VIII levels must be elevated to near normal level of 100%. Since the half-life of factor VIII is 8–12 hours, replacement is needed twice daily in the perioperative period. This requires the use of a factor VIII concentrate infusion and the use of monitors to measure the peak and trough levels repeatedly for the desired level. Alternatively, factor VIII replacement can be given in the form of plasma or cryoprecipitate. Plasma contains 1 unit of procoagulant per milliliter, cryoprecipitate contains 5–10 U/mL, while recombinant concentrates contain up to 40 U/mL. The exposure to plasma derivatives should be minimized and recombinant concentrates are preferable because they do not carry infectious risk.

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Postoperatively, therapy should be continued for up to 2 weeks to avoid any postoperative bleeding. For minor procedure, DDAVP may be effective to release endogenous stores in mild hemophiliac patient. Overtime, repeated factor VIII recombinant concentrates infusion can lead to the production of factor VIII circulating inhibitors. This occurs in 30%–40% of severe hemophiliac patients. There are two types of factor VIII inhibitors, low or high responders. Low responders has low titers of inhibitors thus they can be managed with higher than usual concentrates of factor VIII dosages. High responders have high titers activity and cannot be treated with factor VIII concentrates. Recombinant factor VIIa (rFVIIa) or partially activated prothrombin complex concentrates, such as factor VIII inhibitor bypass ...

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