Daniel A. Handel
HEMOPHILIA
EPIDEMIOLOGY
Hemophilia A (factor VIII deficiency) occurs in about 1:10,000 male births.
Hemophilia B, or Christmas disease, is a factor IX deficiency and occurs in 1:25,000 to 35,000 male births.
PATHOPHYSIOLOGY
Hemophilia is an inherited disorder of a circulating coagulation protein. Hemophilia A and B are X-linked, recessive disorders, and therefore affect males almost exclusively.
Deficiency or defect of the factor VIII or IX protein results in abnormal intrinsic coagulation pathway function.
CLINICAL FEATURES
Patients with hemophilia are categorized as having mild (5-40% of normal factor function), moderate (1-5% of normal function), or severe (<1% of normal function) disease.
Hemophilia is characterized by easy bruising and bleeding into the muscles and joints.
The extent, severity, and frequency of bleeding are dependent on the severity of disease (mild, moderate, or severe).
Trauma, surgical procedures, and spontaneous retroperitoneal or central nervous system bleeding may be life threatening. Traumatic bleeding may be delayed for several hours.
Unless there is another underlying disease, patients with hemophilia do not have problems with minor cuts and abrasions.
Compartment syndrome may result from extremity hematoma.
DIAGNOSIS AND DIFFERENTIAL
Laboratory testing in patients with hemophilia most often shows a normal prothrombin time (PT), prolonged partial thromboplastin time (PTT), and normal bleeding time (BT).
If more than 30% to 40% of factor activity is present, the PTT may be normal.
Specific factor assays may be used to differentiate between the types of hemophilia.
Approximately 10% to 25% of patients with hemophilia A and 1% to 2% of patients with hemophilia B will develop an inhibitor, which is an antibody against the deficient factor.
An inhibitor is diagnosed by mixing the patient’s plasma 50:50 with plasma of a normal control and finding that the mixture still has a prolonged PTT. The quantity of inhibitor is measured by the Bethesda inhibitor assay (BIA) and is reported in BIA units.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
For major or life-threatening bleeding, the mainstay of therapy is factor replacement (Table 137-1).
The management of less severe bleeding depends on the severity of hemophilia, presence or absence of inhibitor, and site and severity of bleeding. Replacement guidelines can be found in Table 137-2.
For severe bleeding the desired factor level is 80% to 100%. For less severe bleeding, the desired factor level is 30% to 50%.
The amount of factor VIII (FVIII) required is determined by: (Target FVIII − Baseline FVIII)/2 × weight (kg).
The amount of factor IX (FIX) required is determined by: (Target FIX − Baseline FIX) × weight (kg).
If factor concentrate is unavailable, or if the type of hemophilia is unknown, fresh frozen plasma (FFP) should be administered. Each milliliter of FFP contains 1 unit of factor VIII. Volume constraints make complete replacement with FFP difficult.
Desmopressin (DDAVP) may be used to raise factor VIII levels in patients with mild to moderate hemophilia A and no inhibitor.
VON WILLEBRAND’S DISEASE
EPIDEMIOLOGY
Von Willebrand’s disease (vWD) is the most common inherited bleeding disorder, occurring in 1% of the population. However, only 1 in 10,000 people manifests a clinically significant bleeding disorder.
PATHOPHYSIOLOGY
Von Willebrand’s factor (vWF) is a cofactor for platelet adhesion as well as a carrier protein for factor VIII, protecting factor VIII from proteolytic degradation.
When exposed to the subendothelial matrix, vWF undergoes a structural change, allowing it to bind to glycoprotein lb. This leads to platelet activation and adhesion to other platelets and to the damaged endothelium.
TABLE 137-1 Replacement Factor Products for Hemophilia Treatment
TABLE 137-2 Initial Factor Replacement Guidelines in Severe Hemophilia
CLINICAL FEATURES
There are three main types of vWD. Type I (70-80% of cases) is a mild form with bleeding episodes usually manifesting as epistaxis, easy bruising, menorrhagia, or dental bleeding. Type II is a qualitative disorder accounting for about 10% to 15% of cases.
Type III is a severe form accounting for less than 10% of cases. These patients manifest with severe bleeding episodes that may resemble the hemophilias (hemarthrosis and hematomas).
Unlike patients with hemophilia, patients with vWD often present with skin and mucosal bleeding. Hemarthrosis is not typical unless severe disease (type III) is present.
In mild cases of vWD, the patient may not be aware of their disease until a traumatic episode or surgical procedure.
DIAGNOSIS AND DIFFERENTIAL
In patients with vWD, the PT and PTT are usually normal. The BT is prolonged and vWF activity is low.
Occasionally, the PT and factor VIII level may be abnormal, making it difficult to distinguish vWD from hemophilia A.
EMERGENCY DEPARTMENT CARE AND DISPOSITION
For most patients with vWD, DDAVP is the mainstay of treatment.
DDAVP works by stimulating endothelial cells to secrete stored vWF, and possibly by promoting hemostasis via additional endothelial effects.
The dose of DDAVP is 0.3 microgram/kg IV or SC over 30 minutes every 12 to 24 hours for up to four doses. The dose of the concentrated intranasal form of DDAVP is one spray in one nostril (150 micrograms) for children over 5 years of age and one spray in each nostril (300 micrograms) for adolescents and adults.
For type 1 patients who do not respond to DDAVP or for patients with type II or III disease, factor VIII concentrate that has a significant concentration of vWF is required.
Cryoprecipitate also contains high concentrations of vWF and may be used to treat patients with vWD. There is, however, a greater risk of viral transmission.
Platelet transfusions may benefit patients with certain types of vWD (type 3) who do not respond to plasma products.
For women with vWD and menorrhagia, birth control pills may help increase the vWF levels and limit the menstrual bleeding.
For further reading in Tintinalli’S Emergency Medicine: A Comprehensive Study Guide, 7th ed., see Chapter 230, “Hemophilias and von Willebrand Disease,” by William Manson, Robin R. Hemphill, and Christine L. Kempton.