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A patient is evaluated for a bleeding disorder if symptoms or signs of unusual or excessive bleeding are present or if a laboratory test abnormality suggesting a bleeding disorder is found incidentally. Patients can also have disorders that produce excessive thrombosis (see Thrombotic Disorders). Unusual or excessive bleeding includes unexplained nosebleeds (epistaxis), excessive or prolonged menstrual blood loss (menorrhagia), prolonged bleeding after minor cuts or trauma, easy bruising into tissues (ecchymoses) or skin (petechial or purpuric lesions), and unexplained gingival bleeding after tooth brushing or flossing.
Systemic bleeding can result from defects in blood vessels (eg, connective tissue diseases, vitamin C deficiency, hereditary hemorrhagic telangiectasia) or, more commonly, quantitative or qualitative disorders of platelets (see Thrombocytopenia and Platelet Dysfunction) or of coagulation (see Coagulation Disorders).
Defects in platelets or blood vessels cause bleeding from superficial sites, including skin and mucous membranes; the bleeding may be spontaneous or may occur immediately after trauma. In contrast, patients with defects in coagulation (coagulopathies) bleed into tissues (eg, hemarthroses, muscle hematomas, retroperitoneal hemorrhage); after trauma, the bleeding may be delayed.
Evaluation
History:
The history should address systemic diseases associated with defects in platelets or coagulation; ingestion of drugs, including aspirin , NSAIDs, or other OTC drugs that impair platelet function; excessive or unusual prior bleeding; and family history of bleeding disorders. A history of excessive or unusual prior bleeding, especially bleeding from multiple sites, suggests thrombocytopenia or a coagulopathy. Absence of a family history of excessive bleeding does not exclude an inherited coagulopathy (eg, hemophilia).
Physical examination:
Signs of skin and mucous membrane bleeding include petechiae, which are pinpoint cutaneous hemorrhages that appear most conspicuously over dependent extremities (especially common in severe thrombocytopenia), ecchymoses, purpura, GI or GU tract bleeding, epistaxis, and hemoptysis. Signs of bleeding from deeper tissues may include joint tenderness and swelling, muscle bruises, and, if severe, signs of intracranial bleeding, hypovolemia, or hemorrhagic shock.
Testing:
Laboratory testing of coagulation is most likely to be abnormal in patients whose history or examination reveals a bleeding risk. Abnormal results in a patient with no signs or symptoms of excessive bleeding should be repeated to exclude laboratory error. Abnormal results are not always clinically meaningful. For example, patients with deficiencies of factor XII, prekallikrein, or high mol wt kininogen in the intrinsic pathway do not bleed excessively (see Table 2: Hemostasis: Laboratory Tests of Hemostasis  ).
Screening tests evaluate the components of hemostasis, including the number of circulating platelets and the plasma coagulation pathways. The most common screening tests for bleeding disorders are the platelet count, PT, and PTT. If results are abnormal, a specific test can usually pinpoint the defect. Determination of the level of fibrin degradation products measures in vivo activation of fibrinolysis.
The PT screens for abnormalities in the extrinsic and common pathways of coagulation (plasma factors VII, X, V, prothrombin, and fibrinogen). The PT is reported as the international normalized ratio (INR), which reflects the ratio of the patient's PT to the laboratory's control value; the INR controls for differences in reagents among different laboratories. Because commercial reagents and instrumentation vary widely, each laboratory should determine its own normal range for PT and PTT; a typical normal range for the PT is between 10 and 13 sec. An INR > 1.5 or a PT ≥ 3 sec longer than a laboratory's normal control value is usually abnormal and requires further evaluation. The INR is valuable in screening for abnormal coagulation in various acquired conditions (eg, vitamin K deficiency, liver disease, disseminated intravascular coagulation). It is also used to monitor therapy with the oral vitamin K antagonist, warfarin .
Partial thromboplastin time (PTT) screens plasma for abnormalities in factors of the intrinsic and common pathways (prekallikrein; high mol wt kininogen; factors XII, XI, IX, VIII, X, and V; prothrombin; fibrinogen). The PTT tests for deficiencies of all clotting factors except factor VII (measured by the PT) and factor XIII. A normal range of 28 to 34 sec is typical. A normal result indicates that at least 30% of all coagulation factors in the pathway are present in the plasma. Heparin prolongs the PTT, and the PTT is often used to monitor heparin therapy. Inhibitors that prolong the PTT include an autoantibody against factor VIII (see Coagulation Disorders: Hemophilia; see Coagulation Disorders: Coagulation Disorders Caused by Circulating Anticoagulants) and antibodies against protein-phospholipid complexes (“lupus anticoagulant”—see Coagulation Disorders: Coagulation Disorders Caused by Circulating Anticoagulants; see Thrombotic Disorders).
Prolongation of the INR or PTT may reflect factor deficiency or the presence of an inhibitor of a component of the coagulation system. The PT and PTT do not become prolonged until one or more of the clotting factors tested are about 70% deficient. For determining whether prolongation reflects a deficiency of one or more clotting factor or the presence of an inhibitor, the test is repeated after mixing the patient's plasma with normal plasma in a 1:1 ratio. Because this mixture provides about 50% of normal levels of all coagulation factors, failure of the mixture to correct the prolongation almost completely suggests the presence of an inhibitor in patient plasma.
Use of the bleeding time as a screening test to assess platelet–vessel wall interactions is of doubtful reliability. The test is performed with a BP cuff inflated to 40 mm Hg on the upper arm. A disposable spring-loaded device is used to make a standardized incision on the volar aspect of the forearm. Blood is absorbed onto filter paper at 30-sec intervals until bleeding stops. The bleeding time may be prolonged by thrombocytopenia, disorders of platelet function, von Willebrand's disease (VWD), and, unlike other laboratory tests, primary vessel wall abnormalities. Use of aspirin within 7 days also may prolong the bleeding time. Theoretically, the bleeding time is not prolonged by inherited or acquired coagulation disorders; in practice, however, results are unpredictable in these conditions. Because the sensitivity and reproducibility of the bleeding time are limited, its use is controversial.
Normal results on all of the screening tests exclude many bleeding disorders. Exceptions include rare, severe factor XIII deficiency, which requires a specific assay if suspected; VWD, a common entity in which the associated deficiency of factor VIII is frequently insufficient to prolong the PTT; and rare disorders of fibrinolytic control. Because prolongation of the PT or PTT requires about 70% deficiency of one or more coagulation factors, suspicion of less severe factor deficiencies (eg, patients with mild bleeding disorders) requires performance of more sensitive assays of specific factors.
In patients with bleeding disorders and symptoms suggesting occult bleeding, evaluation should be thorough. For example, CT scanning should be used for patients with severe headaches, head injuries, impairment of consciousness, or possible intraperitoneal or retroperitoneal hemorrhage.
Treatment
Treatment is directed at the underlying cause and at complications of bleeding (see Lacerations: Closure for control of localized bleeding and see Shock and Fluid Resuscitation: Hemorrhagic shock for treatment of hemorrhagic shock). For immediate treatment of bleeding due to a coagulopathy that has not yet been diagnosed, fresh frozen plasma, which contains all coagulation factors, should be infused pending definitive evaluation.
Last full review/revision November 2005
Content last modified November 2005
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