Clinical Aspects of and Therapy for Hemophilia B. Harold R. Roberts and T, Flint Gray III, страница 3

Soft Tissue Hemorrhage

Soft tissue hemorrhage in hemophilia B may be mild and uncomplicated, as in a small localized hematoma, but must be treated with care due to the risk of progression via dissection and resultant serious complications. Large dissecting hematomas can occur rapidly in a matter of hours or slowly over a period of days. Soft tissue hemorrhages may be particularly dangerous when occult dissection into enclosed areas occurs. For example, major blood loss and compromise of vital structures may occur when hemorrhage into the retroperitoneal space dissects inferiorly into the femoral canal or superiorly through the diaphragm and thoracic cavity. Significant blood loss can also be concealed in the soft tissues of the limbs. Hemorrhage in the oropharynx or neck that initially appears to be minor is particularly dangerous since it may rapidly enlarge to compress the airway and threaten life. These complications can be most easily recognized if they are considered in the course of a careful evaluation; they can usually be prevented by prompt treatment of minor hemorrhages.

Hematuria

Most patients with severe hemophilia B will experience hematuria during their lifetimes. Gross hematuria occurs frequently and sometimes leads to significant blood loss. On the first occasion, gross hematuria should be evaluated with appropriate diagnostic studies, but most often a structural lesion will not be found. Subsequent episodes of hematuria do not require extensive restudy. Small, occult erosions of the renal pelvis may sometimes cause such hematuria. The most common complication of hematuria is renal colic caused by ureteral obstruction with clots. Hematuria is sometimes self-limited to a few days, but it may persist for weeks or months if untreated.

Laboratory Evaluation and Differential Diagnosis

The clinical diagnosis of hemophilia B should be considered in any male with a lifelong history of crippling hemarthroses and in any infant with evidence of abnormal bleeding. Mild or moderate hemophilia B should be considered in any person with abnormal surgical bleeding or hematoma formation out of proportion to injury. Hemarthrosis in a patient with a prolonged partial thromboplastin time (PTT) suggests the diagnosis of either hemophilia A or hemophilia B. Definitive diagnosis of hemophilia B requires a specific assay for factor IX. The prothrombin time (PT), thrombin time, and bleeding time are usually normal. However, there is a variant of hemophilia B, termed hemophilia BM (subscript referring to the index family surname, Martin), characterized by an abnormal ox-brain PT as well as a prolonged PTT. 23 The usual PT, performed with rabbit or human brain thromboplastin, is normal or only slightly prolonged. The molecular biology of this variant has been well studied, suggesting that the prolonged ox-brain PT may result from competitive inhibition of factor VII by factor IX for the substrate, factor X. MLID89135000 MLID82250782  24–26

Screening tests of coagulation may be normal in mild or even moderate hemophilia B since as little as 20–30% of normal levels of factor IX activity may be sufficient to yield a normal PTT. Thus, the patient's clinical and family history of hemorrhage, with particular attention to a history of bleeding after surgical procedures and dental extractions, is a more reliable indicator of a bleeding disorder than screening tests of clotting function (such as the PTT and PT). Hemophilia B is distinguished from acquired coagulopathies on the basis of its lifelong symptoms and its sex-linked transmission within an involved kindred. A lack of family history does not rule out the diagnosis, however, since approximately one-third of mutations occur de novo.