Page 2148 - Williams Hematology ( PDFDrive )

2122 Part XII: Hemostasis and Thrombosis Chapter 123: Hemophilia A and Hemophilia B 2123

threefold above baseline in most, but not all, mildly or moderately quantities of fluids. If hematuria is mild, uncomplicated, and painless,
affected hemophilia A patients. Patients with severe hemophilia A do factor VIII replacement may not be necessary unless the hematuria
not respond to DDAVP. A concentrated intranasal spray of DDAVP persists. Gross or protracted hematuria requires replacement therapy.
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also can be used (150 mcg in each nostril for adults and 150 mcg in one In these patients, factor VIII levels of at least 50 percent of normal or
nostril for children weighing less than 50 kg). The degree of response higher are needed, probably because urine is rich in urokinase that rap-
to the drug should always be determined in patients before a bleeding idly lyses clots.
episode, because occasionally mildly or moderately affected patients Hemophilic patients requiring endoscopic procedures first
do not respond. The peak response to DDAVP usually occurs 30 to should be treated with factor VIII to raise levels to at least 0.5 U/mL
60 minutes after dosing. In patients with mild or moderate hemophilia before the procedure. Only one dose may be necessary if endoscopy
A and in carriers whose baseline factor VIII levels are less than 0.5 U/mL, is uncomplicated. In cases of biopsies, severe abrasions or perforations
DDAVP may be used in lieu of blood products. The mechanism by following endoscopy, factor VIII replacement should be continued until
which DDAVP increases factor VIII is unknown. healing of the lesion is complete. For expanding soft-tissue hematomas,
Repeated administration of DDAVP results in a diminished factor VIII therapy should be started immediately and maintained until
response to the agent (tachyphylaxis). In many patients, the response the hematoma begins to resolve. With effective therapy, the patient usu-
to the second DDAVP dose averages 30 percent less than the response ally experiences rapid relief from pain. For treatment of acute hemar-
to the first dose, and the response rate may be even less after additional throses, prompt administration of factor VIII decreases the occurrence
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doses. DDAVP is a potent antidiuretic. As a result, hyponatremia has of extensive degenerative joint changes, deformity, and muscle wasting.
been reported in some patients whose water intake exceeds approxi- For chronic synovitis and for bleeding into “target” joints, daily admin-
mately 1 L per 24 hours after dosing. There is no convincing evidence to istration of factor VIII to raise levels to 100 percent of normal for 6 to
indicate that DDAVP administration is associated with thrombosis in 8 weeks (“secondary prophylaxis”) is usually indicated.
hemophilic patients.
Treatment of Major Nonsurgical Hemorrhages
Antifibrinolytic Agents Any hemorrhage in a patient with hemophilia A may become major, but
Antifibrinolytic agents, such as ε-aminocaproic acid (EACA) and the following hemorrhages are common and frequently life-threatening:
tranexamic acid, have been used to enhance hemostasis in patients retropharyngeal, retroperitoneal, and central nervous system bleeding,
with hemophilia A. 53,54 Fibrinolytic inhibitors may be given as adjunc- whether subdural, subarachnoid, or into the brain parenchyma. 56
tive therapy for bleeding from mucous membranes and are particularly For treatment of retropharyngeal bleeding, particularly that asso-
valuable as adjunctive therapy for dental procedures. The usual oral ciated with a sensation of tightness in the throat, pain in the neck,
dose of tranexamic acid for adults is 1 g four times per day. EACA can dysphagia, or difficulty breathing, patients should receive factor VIII
be given as a loading dose of 4 to 5 g followed by 1 g/h by continu- immediately in doses sufficient to raise factor VIII levels to normal
ous IV infusion in adults. Another regimen of EACA is 4 g every 4 to (1.0 U/mL). Near-normal levels should be maintained until bleeding
6 hours orally for 2 to 8 days, depending upon the severity of the bleeding ceases and the hematoma begins to resolve. For retroperitoneal hemor-
episode. Antifibrinolytic therapy is contraindicated in the presence of rhage, early treatment is required, and therapy should be continued for
hematuria because clots resistant to lysis may obstruct the ureters. 7 to 10 days; otherwise, bleeding may recur upon resumption of activity.
Immediate administration of factor VIII, sufficient to raise the
Fibrin Glue level to normal, should be started upon the first sign of an intracra-
Fibrin glue, otherwise known as fibrin tissue adhesive, has been used nial hemorrhage or following a history of head trauma. Even asymp-
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as adjunctive therapy to factor VIII in hemophilic patients. Briefly, tomatic patients with a history of head trauma should receive at
fibrin glue contains fibrinogen, thrombin, and factor XIII. Fibrinolytic least one dose of factor VIII as a prophylactic measure, and this dose
inhibitors are added to some commercial products. The fibrinogen– should be given before diagnostic procedures such as a CT scan. Treat-
factor XIII mixture is placed on the injury site and clotted with a human ment of a known intracranial hemorrhage should be maintained for a
thrombin solution containing calcium. As a result, the fibrin clot is minimum of 7 to 10 days, and the circulating factor VIII level should be
crosslinked and anchored to tissue. It is especially useful for hemostasis kept normal throughout this period. Prolonged secondary prophylaxis
in patients undergoing dental surgery who receive a preextraction bolus is often indicated following an intracerebral hemorrhage, particularly
of factor VIII followed by application of fibrin glue to the tooth socket. in patients with HIV disease, who seem to have a high recurrence rate.
Fibrin glue also has been used as adjunctive therapy to factor VIII Evacuation of subdural hematomas and surgical removal of hematomas
following orthopedic procedures and circumcision. It is very valuable involving the brain parenchyma can be performed, depending upon
for controlling bleeding when applied to the bed of a surgical wound location. Despite aggressive replacement therapy, however, mortality from
following removal of large pseudotumors. Some hemophilia centers central nervous system bleeding is high.
prepare their own “homemade” fibrin glue using cryoprecipitate as a
source of fibrinogen and factor XIII. Replacement of Factor VIII for Surgical Procedures
For major surgical procedures, factor VIII should be raised to normal
Treatment of Minor or Moderate Hemorrhage levels before operation and maintained for 7 to 10 days or until heal-
On occasion, superficial cuts and abrasions are managed with local ing is complete. Treatment can be started a few hours before surgery
measures, that is, application of pressure sometimes suffices to con- and continued intraoperatively using a continuous infusion or boluses
trol bleeding, although oozing may continue intermittently for several every 8 to 12 hours. Postoperatively, factor VIII levels should be mon-
hours. Topical thrombin is of little value in this type of bleeding. In gen- itored at least one or two times per day to ensure that adequate levels
eral, cautery should be avoided because bleeding may restart when the are maintained. Because factor VIII may be “consumed” during surgery,
cauterized area is sloughed. factor VIII levels should be monitored intraoperatively and doses of
When replacement therapy for epistaxis is needed, the factor VIII factor VIII higher than normal may be required. Bone and joint sur-
level should be raised to approximately 30 to 50 percent of normal. For gery may require longer periods of factor VIII coverage. Replacement
treatment of hematuria, patients should be instructed to drink large of knee, hip, ankle, and elbow joints may be required for intractable

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