Page 2004 - Hematology_ Basic Principles and Practice ( PDFDrive )

1778 Part XI Transfusion Medicine

virally inactivated but has the drawback of exposing the patient to a less common than with severe hemophilia. Correlation between
large number of donors (2500) with each dose. bleeding and factor V levels is poor. No factor V–enriched plasma
concentrates are available. Because factor V is in the common pathway
of coagulation, in deficiency states, both the PT and the aPTT are
Fibrinogen Deficiency prolonged. Treatment of bleeding involves the infusion of plasma at
15–20 mL/kg with a goal of achieving levels of 20%. The half-life of
Bleeding disorders can result from low to absent levels of fibrinogen factor V is approximately 36 hours. Because platelets contain stored
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(hypofibrinogenemia or afibrinogenemia) or a protein with abnormal factor V, they have been used to treat bleeding. Platelet infusion
function (dysfibrinogenemia). The inheritance pattern for the former may result in the production of platelet-specific antibodies.
is autosomal recessive and for the latter is autosomal dominant.
Dysfibrinogenemias can result in bleeding or hypercoagulability. The
gene for fibrinogen is located on chromosome 4. Because fibrinogen Factor VII Deficiency
is required for the formation of a fibrin clot, it is surprising that
afibrinogenemic patients survive gestation and birth. Diagnosis is Factor VII deficiency occurs in approximately 1 : 500,000 people; it
made when patients present with bleeding from the umbilical stump, is autosomal recessive and of the rare inherited coagulation disorders,
intracranial hemorrhage, or mucosal bleeding. Hemarthroses can factor VII deficiency is the most common. Severe bleeding occurs
occur but are less common than observed with the hemophilias. with levels below 1%, and symptoms in severely affected patients are
Wound healing may be delayed. Increased incidence of fetal wastage similar to those observed with severe hemophilia. Intracranial hemor-
in patients with afibrinogenemia and hypofibrinogenemia is observed, rhage may occur in up to 16% of cases and in neonates after vaginal
and term gestation is rarely achieved without replacement of delivery. The PT is prolonged, but the aPTT and thrombin time are
fibrinogen. 116–118 Because the substrate for clot formation, fibrinogen, normal. PCCs contain factor VII and may provide a benefit over
is missing or deficient, the prothrombin time (PT), activated partial plasma because they are virally inactivated. As with the use of these
thromboplastin time (aPTT), thrombin clotting time (TCT), and products for factor VIII and factor IX inhibitors, thrombosis has been
coagulation assays that have fibrin formation as their end points are reported. Several plasma-derived factor VII concentrates (LFB, Baxter
all prolonged. Replacement of fibrinogen is accomplished with and PFL) have been developed and have been used to treat congenital
cryoprecipitate with a goal of achieving a plasma level between 50 deficiency. Recombinant activated factor VII concentrate is effective
and 100 mg/dL and at least 60 mg/dL for maintenance of preg- in the treatment of bleeding with a congenital factor VII
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nancy. Each bag of cryoprecipitate contains approximately 200 to deficiency. 122–125 This can be used at a dose of 10–40 µg/kg every 4–6
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300 mg of fibrinogen. The biologic half-life of fibrinogen is between hours. Inhibitors to factor VIIa have developed in patients with
2 and 4 days. Virally inactivated, highly purified fibrinogen concen- congenital factor VII deficiency. 122
trates are available in Europe, China, and Japan (Japan Green Cross,
Aventis, LFB) and in the United States, RiaSTAP, CSL Behring is
available. These fibrinogen concentrates offer many advantages over Factor X Deficiency
cryoprecipitate, including: viral inactivation, standardized fibrinogen
content, smaller infusion volume and expedited time to treat the Congenital deficiency of factor X is a rare condition resulting from
patient as reconstitution is swift, since it is stored as a lyophilized homozygous or compound heterozygous defects in the autosomal
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powder, and there is no need for cross-matching. Adverse reactions genes for factor X located on chromosome 13. Bleeding is correlated
to treatment include the development of fibrinogen antibodies; with factor X levels, and symptoms include epistaxis, menorrhagia,
allergic reactions; and, paradoxically, thrombosis. hemarthrosis, intracranial or gastrointestinal hemorrhage, hematuria,
and umbilical cord bleeding. Because factor X is a component of
prothrombinase (the first step in the common pathway), diagnosis is
Prothrombin Deficiency suggested by both a prolonged PT and a prolonged aPTT but a
normal TCT. Treatment is with plasma products (FFP or S/D-treated
Congenital prothrombin deficiency is a rare autosomal recessive plasma) at approximately 15–25 mL/kg followed by 5 mL/kg every
disorder estimated to be present at a rate of 0.5 cases per million. 24 hours with a goal of plasma factor X activity levels of 20%. PCCs
Disease has been described with both homozygous and heterozygous can be used; however, they contain variable amounts of factor X. As
defects (including compound heterozygotes). No reports of a pro- with the use of PCCs for other indications, the risk of thrombosis is
thrombinemia appear in the literature, suggesting that complete lack increased. Currently, a Phase III, multicenter study to investigate the
of the protein is incompatible with normal development. Hemor- pharmacokinetics, safety, and efficacy of a high purity factor X (Bio
rhagic symptoms include bruising; hemarthroses; intracranial, Products Laboratory) in patients with moderate to severe factor X
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mucosal, and deep tissue bleeding; and menorrhagia. Correlation deficiency was completed and results are not yet available. 127
between bleeding and prothrombin levels is poor. Both the PT and
the aPTT are prolonged, and the thrombin time is normal. Treatment
of prothrombin deficiency includes plasma at a dose of 15–25 mL/ Factor XI Deficiency
kg followed by 3 mL/kg every 12–24 hours to achieve levels of
approximately 30%. The half-life of prothrombin is approximately 3 Congenital factor XI deficiency (sometimes called hemophilia C) is
days. PCCs contain prothrombin and other VKD factors and can be an autosomal disorder with a recessive pattern of inheritance and is
used to treat prothrombin-deficient patients who are undergoing particularly common in Ashkenazi Jews in whom two specific muta-
major surgery or life-threatening bleeds. Caution should be exercised tions account for the approximately 8% prevalence of an abnormal
because these have been associated with thrombosis. factor XI gene. 123,124 The factor XI gene is located on chromosome 4.
Bleeding symptoms are variable and include postsurgical or traumatic
bleeding or heavy menses in women. Spontaneous hemorrhage and
Factor V Deficiency musculoskeletal bleeding are not typical of the disorder, and these
characteristics distinguish this disorder from hemophilia A and B.
Inherited deficiency of factor V occurs in fewer than 1 : 1,000,000 Plasma levels of factor XI do not correlate with bleeding symptoms
people with an autosomal recessive inheritance pattern (homozygous unlike the factor levels in hemophilia A and B. The aPTT is prolonged
or compound heterozygous), resulting in factor V levels less than with factor XI deficiency; PT and thrombin time are normal.
20%. Symptoms include bleeding from the umbilical stump and Patients with factor XI deficiency are usually treated before surgical
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mucous membranes, ecchymoses, menorrhagia, postpartum bleed- procedures with a goal of factor XI levels between 30 and 45 U/dL.
ing, and intracranial hemorrhage. Hemarthroses can occur but are Plasma (FFP and S/D-treated plasma) provides the mainstay of