Thrombocytopenia - Diagnosis and Management

Clinical Manifestations

            There is no strong correlation between the severity of bleeding and the number of platelets. Multiple factors play a role. A patient with immune thrombocytopenic purpura may not bleed even if the platelet count is < 10,000/mcl due to very functional platelets. On the other hand, a patient with mild thrombocytopenia may develop significant bleeding if he/she is on medications like heparin, aspirin or pentoxyfilline. Renal failure sepsis, coagulopathy from any cause can be contributory as well. The common clinical presentations of thrombocytopenia are listed in Table 5. Serious bleeding such as spontaneous intracranial bleeding is very rare unless the platelet count is less than 10,000/mcL

Table 5. Common clinical presentations of thrombocytopenia

Petichial hemorrhages

Echymoses or bruising

Wet purpura, bleeding from mucus membranes of the mouth

Bleeding from nose, gums, hematuria, or heavy menstrual flow in females, etc.

Diagnosis

    Step 1:

Review complete blood count (CBC) carefully. High mean platelet volume or mean platelet volume (MPV) (like mean corpuscular volume (MCV) for red blood cells) indicates large platelets, which occurs in pseudo thrombocytopenia, peripheral destruction of platelets or splenic sequestration. Isolated thrombocytopenia is usually a sign of immune thrombocytopenic purpura. Presence of simultaneous leucopenia and anemia indicate a generalized process such as bone marrow problems, cyanocobalmine or folate deficiency or hypersplenism. High MCV may suggest B12 or folate deficiency, alcohol abuse, or myelodysplastic syndromes. High white blood cell count or blasts may be present in acute or chronic leukemia.

    Step 2:

Review peripheral smear. Make sure that it is not due to platelet clumping, also known as spurious or psuedothrombocytopenia. Attention should be made to the smear with regards to large platelets, schistocytes , hypersegmented as well as hyposegmented neutrophils, blasts, etc.

Blood smear with schistocytes.

    Step 3:

History and physical examination can give clues as well. The following questions should be asked:

               1. Previous history of thrombocytopenia or other blood related problems

               2. Recent infections or illnesses

               3. New medications

               4. Previous blood transfusions

               5. Risk factors for HIV

               6. Alcohol abuse, etc.

               7. Dietary habits Common tests in the diagnosis of thrombocytopenia are shown in Table 6. Anti-platelet or platelet associated antibodies are neither sensitive nor specific. The role of these tests is not well defined. If there is suspicion for TTP/ HUS ordering reticulocyte count, LDH and haptoglobin is highly recommended. HIV and hepatitis tests should be done only if the patient has risk factors.

Table 6. Common tests in the evaluation of thrombocytopenia

Complete blood count with differential

Reticulocyte count

LDH

Haptoglobin

B12, folate and iron levels

Anti-nuclear antibodies

HIV test

Hepatitis B and C antibodies

Platelet associated antibodies

Role of Bone Marrow Biopsy

            Bone marrow aspiration/biopsy is minimally invasive, but usually is associated with pain/ pressure. This should be reserved for patients in whom the above work-up is unrevealing or if there is any suspicion for myelodysplastic syndrome or leukemia. It serves as a confirmatory test in immune thrombocytopenia (increased or adequate number of megakaryocytes), myelodysplastic syndrome (dysmegakaryopoiesis, etc.) or leukemia (increased number of blasts- >20%).  Please refer to Figure1 and Figure 2.

Management

               Treating the underlying cause is the most important intervention. If it is immune thrombocytopenic purpura, start appropriate treatment such as steroids or intravenous immunoglobulin (IVIG). If a drug is a suspect, discontinue the drug and observe. Drug-induced thrombocytopenia is usually immune mediated and is treated as immune thrombocytopenic purpura with steroids and IVIG. Heparin Induced thrombocytopenia (HIT) is potentially life threatening condition. If there is clinical suspicion all heparin must be discontinued and direct thrombin inhibitor (egg. Lepirudin) must be initiated. Plasma exchange must be initiated immediately if TTP is suspected. In HEELP syndrome, often delivery is indicated. HIV related thrombocytopenia often responds to Zidovidine.

               Platelet transfusions are generally reserved for patients who are bleeding or have a platelet counts of <10,000/mcL. The main goal of transfusion is to prevent bleeding. If a patient is undergoing surgery or procedure, the target platelet count should be more than 75,000/mcL. Oprelvekin (Neumega) is an interleukin- 11, which has been shown to reduce the severity of thrombocytopenia due to chemotherapy and the need for platelet transfusions. It is not as widely used as other growth factors (filgastrim, erythropoietin) due to slow response, serious adverse reactions such as hypersensitivity reactions or anaphylaxis, significant fluid retention. The approach for outpatient and in-patient is quite different and is illustrated in Figure1 and Figure 2.