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I HAVE A PATIENT WITH A BLEEDING DISORDER

How do I determine the cause?

CHIEF COMPLAINT

PATIENT image

Ms. A is a 24-year-old woman who comes to see you because her gums are bleeding when she brushes her teeth.

image What is the differential diagnosis of bleeding? How would you frame the differential?

CONSTRUCTING A DIFFERENTIAL DIAGNOSIS

The framework for bleeding distinguishes between structural causes (ie, an injury to the tissue or organ), platelet-related causes, and clotting factor–related causes. Bleeding due to platelet abnormalities, whether due to reduced number or abnormal function of platelets, is usually small vessel bleeding, and produces such findings as petechiae, bruising, gum bleeding, or nosebleeds. The bleeding starts and persists immediately following the injury that induces it. Platelet-related bleeding is generally not quantitatively significant (ie, platelet-related bleeding tends not to cause serious blood loss requiring red cell transfusions). Nonetheless, platelet-­related bleeding can still be clinically important if a patient bleeds a small amount into the brain (unusual unless the platelet count is < 10,000/mcL) or induces an abdominal hematoma from vigorous coughing, for example. By contrast, bleeding due to coagulation factor deficiencies or inhibitors tends to be delayed; that is, a platelet plug slows or stops the bleeding immediately after an injury, but the platelet plug is then not bolstered by the stable fibrin clot that is meant to definitively stop the bleeding. Bleeding due to coagulation factor abnormalities is more likely to be quantitatively significant, generally occurring in joints, the gastrointestinal (GI) tract, brain, retroperitoneum, or at sites of recent injury or medical or surgical intervention.

  1. Structural causes

    1. Tissue injury from trauma

    2. Abnormality of the tissue such that minor trauma causes bleeding, such as a toothbrush causing gum bleeding from inflammatory gingival disease

  2. Bleeding due to platelet disorders

    1. Disorders of platelet number (thrombocytopenia)

      1. Decreased production of platelets

        1. Medications (examples include valproic acid, linezolid, thiazide diuretics, gold compounds, antineoplastic chemotherapy drugs)

        2. Bone marrow replacement by malignancy, fibrosis, granulomas

        3. Bone marrow aplasia

        4. Suppression of megakaryocyte production by heavy alcohol use

        5. Vitamin B12 deficiency (megaloblastic hematopoiesis is a DNA synthetic defect affecting all cell lines, not only erythroid)

      2. Increased loss or consumption of platelets

        1. Splenic sequestration (platelet count usually stays above 40,000/mcL)

        2. Autoimmune thrombocytopenia

          1. Idiopathic (also called idiopathic thrombocytopenic purpura [ITP])

          2. HIV

          3. Systemic lupus erythematosus (SLE)

          4. Lymphoproliferative disorders

          5. Hepatitis C

          6. Medications (examples include heparin, phenytoin, carbamazepine, sulfonamides, quinine, antiplatelet drugs used for coronary syndromes such as abciximab or tirofiban)

        3. Disseminated intravascular coagulation (DIC)

        4. Thrombotic thrombocytopenic purpura (TTP)

        5. Sepsis

    2. Disorders of platelet function

      1. Congenital

        1. von Willebrand disease

        2. Other rare genetic abnormalities

      2. Acquired

        1. Medications, such as aspirin, nonsteroidal anti-inflammatory drugs (NSAIDs). In some instances, the drugs are administered with the intention of inhibiting platelet function, such as aspirin or clopidogrel for cardiovascular disease.

        2. Myeloproliferative disorders, such as essential thrombocythemia, polycythemia vera

        3. Coating of platelets by abnormal proteins, such as in plasma cell myeloma (formerly multiple myeloma) and, occasionally, immune thrombocytopenia

        4. Uremia

  3. Bleeding due to clotting factor abnormalities

    1. Congenital

      1. Hemophilia A (the most common)

      2. Other clotting factor deficiencies

    2. Acquired

      1. Deficiency of a factor or factors

        1. Liver disease

        2. Vitamin K deficiency (nutritional or due to warfarin therapy)

        3. Abnormal adsorption of a factor, eg, factor X adsorption to amyloid fibrils

        4. Consumption of factors, eg, DIC

        5. Dilution of factors, eg, massive transfusion

      2. Acquired inhibitor to clotting factor or factors

Figure 8-1 shows the diagnostic approach to bleeding disorders.

Figure 8-1.

Diagnostic approach to the bleeding patient.

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