Page 2146 - Williams Hematology ( PDFDrive )

2120 Part XII: Hemostasis and Thrombosis Chapter 123: Hemophilia A and Hemophilia B 2121

Functional factor VIII coagulant activity is measured by one-stage of the numerous nonprescription analgesics and herbals that contain
clotting assays based on the aPTT. Chromogenic assays for factor VIII aspirin or other antiplatelet agents. Addictive narcotic agents should be
activity also are used widely, but do not always agree with one-stage used with great caution and only when clearly indicated, because drug
39
assays. Although infrequently measured in practice, factor VIII anti- dependency can be a major problem for patients with hemophilia. In
gen is measured by immunologic assays, which detect normal and most general, intramuscular injections should be avoided unless the patient
abnormal factor VIII molecules. If the factor VIII antigen level is nor- receives adequate replacement therapy. In the absence of prophylactic
mal but the clotting activity is reduced, the patient has a dysfunctional therapy, patients with hemophilia A must be treated as early as pos-
factor VIII molecule. Such patients have antigen-positive hemophilia, sible to avoid bleeding complications. Surgical procedures in hemo-
40
also referred to as cross-reacting material (CRM)-positive. Patients in philic patients should be scheduled early in the week to avoid “weekend
whom both the factor VIII antigen level and activity are nearly unde- crises.” Ample supplies of factor VIII should be available in the blood
tectable are said to be CRM-negative. bank or pharmacy to ensure rapid access to treatment when needed. All
hemophilic patients should have access to home treatment and periodic
DIFFERENTIAL DIAGNOSIS examinations at a comprehensive hemophilia treatment center. Prophy-
VWD sometimes is confused with hemophilia A. The basic defect in lactic therapy is recommended in all severely affected patients, and it
should be initiated before the onset of recurrent hemarthroses (primary
VWD is reduced activity of von Willebrand factor (VWF), which acts prophylaxis) or as directed. Secondary prophylaxis for an established
as a carrier of factor VIII in vivo (Chap. 126). Thus, in VWD, factor VIII “target” joint may be necessary. 45
levels are reduced, although considerable variability exists. Although
factor VIII is synthesized normally in patients with VWD, the half-life
of factor VIII is markedly shortened because the VWF “carrier” mole- Factor VIII Replacement Therapy
cule is decreased or absent. Other abnormalities in VWD that distin- Hemorrhagic episodes in patients with hemophilia A can be managed
guish VWD from hemophilia A are decreased VWF antigen level, and by replacing factor VIII. Several products are available for use in raising
decreased VWF activity, often measured using the ristocetin cofactor factor VIII to hemostatic levels (Table 123–2). Fresh-frozen plasma and
activity assay and a prolonged closure time using the platelet function
analyzer PFA-100. In type III VWD, factor VIII levels may be very low
(<5 percent of normal), making it difficult to distinguish from classical TABLE 123–2. Currently Available Factor VIII Products a
hemophilia. The lack of a sex-linked pattern of inheritance in the family
will help in the differential diagnosis. Origin Viral Inactivation
Another variant of VWD that is particularly difficult to distinguish Intermediate purity
from hemophilia A is VWD-Normandy, in which VWF multimers are b c
normal but plasma factor VIII levels are low. Several mutations caus- Humate P Plasma Pasteurization
41
ing VWD-Normandy have been described, but all of them result in High purity
decreased binding of factor VIII to VWF. The result is shortening of the Koate DVI b Plasma Solvent-detergent , heat
42
d
intravascular survival of factor VIII and thus reduced factor VIII activity. Alphanate b Plasma treated i
The Normandy variant of VWD should be suspected in patients with Solvent-detergent, heat
mild hemophilia A who do not exhibit a sex-linked recessive inheri- treated i
tance pattern. Ultrapure e
Hemophilia A must be distinguished from other hereditary blood
clotting factor deficiencies that exhibit a prolonged aPTT, including defi- Hemofil M Plasma Solvent-detergent d
ciencies of factors IX, XI, and XII, prekallikrein, and high-molecular- Monoclate P Plasma Pasteurization c
weight kininogen. Only deficiencies of factors VIII and IX cause chronic Recombinant
crippling hemarthroses with a family history suggestive of an X-linked h f d
bleeding disorder. Only specific assays can distinguish hemophilia A Advate CHO cells Solvent-detergent
from factor IX deficiency (hemophilia B). Factor XI deficiency occurs Recombinate e CHO cells f
in males and females and is a milder hemorrhagic disorder compared Kogenate FS e BHK cells g Solvent-detergent
to severe hemophilia A or B. Factor XI deficiency can be confused with Helixate FS e BHK cells g Solvent-detergent
mild hemophilia A or B on screening laboratory tests, but specific assays Xyntha h CHO cells f Solvent-detergent,
distinguish them. Deficiencies of factor XII, prekallikrein, and high-mo- nanofiltration
lecular-weight kininogen can be distinguished from hemophilia because Eloctate* h HEK cells J Solvent-detergent
they are not associated with bleeding. Mild hemophilia A, with factor
VIII levels of approximately 10 to 20 percent of normal, must be distin- *Extended half-life FVIII product.
guished from combined deficiency of factors V and VIII. 43,44 Both the PT a Additional concentrates are available in Europe.
and aPTT are moderately prolonged in the combined disorder. 44 b Contains von Willebrand factor (VWF).

c Pasteurization at 60°C for 10 hours.
THERAPY d Solvent-detergent: tri-n-butyl phosphate (TNBP) + polysorbate 80.
General e Human albumin added; insignificant VWF.
General principles applicable to therapy for hemophilia A include f Chinese hamster ovarian cells.
avoidance of aspirin, nonsteroidal antiinflammatory drugs, and other g Baby hamster kidney cells.
agents that interfere with platelet aggregation. Acetaminophen or rel-
atively specific cyclooxygenase (COX)-2 inhibitors such as celecoxib h Not exposed to human or animal protein during manufacture.
have been recommended, but these drugs can be harmful when taken i Heat treated at 80°C for 72 hours.
in excessive doses or for prolonged periods. Patients should be advised J Human embryonic kidney cells.

Kaushansky_chapter 123_p2113-2132.indd 2121 9/21/15 4:36 PM