Thrombocytopenia resident survival guide

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ogheneochuko Ajari, MB.BS, MS [2]

Overview

Thrombocytopenia is the decreased concentration of platelets below 150,000 cells per microliter of blood.

Causes

Life Threatening Causes

Life-threatening causes include conditions which may result in death or permanent disability within 24 hours if left untreated.

• Disseminated intravascular coagulation
• HELLP syndrome

Common Causes

• Abruptio placentae
• Bone marrow suppression (chemotherapy, irradiation)
• Cardica bypass
• Chronic alcohol use
• Chronic liver disease
• Common variable immunodeficiency
• Congenital thrombocytopenia
• Connective tissue disorders (eg SLE, RA, antiphospholipid syndrome)
• Disseminated intravascular coagulation
• GP IIb/IIIa inhibitor
• Hemolytic uremic syndrome
• Heparin-induced thrombocytopenia
• Immune thrombocytopenic purpura
• Infections
• Macrophage-activation syndrome
• Medications
• Preeclampsia
• Pregnancy
• Pseudothrombocytopenia
• Thrombotic thrombocytopenic purpura

Management

Shown below is an algorithm depicting the initial approach to thrombocytopenia.

Characterize the symptoms: ❑ Onset (acute, chronic, recurrent) ❑ Easy bruising ❑ Petechia ❑ Rashes ❑ Melena ❑ Fevers ❑ Bleeding ❑ Headaches ❑ Abdominal pain ❑ Visual disturbances ❑ Weight loss ❑ Night sweats ❑ Bone pain Obtain a detailed history: ❑ Recent medications ❑ Pregnancy ❑ Family history ❑ Malignancy ❑ Recent infection ❑ Recent vaccinations ❑ Recent travels ❑ Recent transfusions ❑ Chronic alcohol use ❑ Recent hospitalization ❑ Recent organ transplantation ❑ Recent valve replacement surgery ❑ Dietary habits ❑ Sexual history ❑ Ingestion of quinine containing beverages

Examine the patient: ❑ Bleeding location ❑ Bleeding severity ❑ Hepatomegaly ❑ Splenomegaly ❑ Mucocutaneous bleeding ❑ Skeletal abnormalities ❑ Joint or soft tissue bleeding ❑ Rash ❑ Generalized lymphadenopathy ❑ Skin necrosis ❑ Neurological exam

Order tests: ❑ Peripheral blood smear ❑ CBC and differential ❑ Reticulocyte count ❑ LDH ❑ LFT ❑ Renal function test ❑ Clotting screen ❑ PT ❑ aPTT ❑ Fibrinogen ❑ Haptoglobin ❑ D-dimer ❑ Request a hematology consult

❑ Order additional tests based on the results of the CBC-D and peripheral blood smear

Possible Pseudothrombocytopenia ❑ Clumped platelets

True thrombocytopenia

❑ Order platelet count on heparinized blood specimen

Isolated thrombocytopenia

Thrombocytopenia with abnormalities in other blood lineages

Guide your next step by specific findings

Consider: ❑ ITP ❑ Drug induced thrombocytopenia ❑ HIV ❑ HCV ❑ H. pylori ❑ DIC ❑ Gestational thrombocytopenia

Look for: ❑ Schistocytes ❑ Spherocytes ❑ Dacrocytes ❑ Blasts ❑ Giant platelets ❑ Granulations ❑ Hypersegmented neutrophils ❑ Macrocytosis ❑ Lymphocytosis ❑ Neutropenia

Note that the treatment of thrombocytopenia is specific to the underlying cause of thrombocytopenia.

Diagnostic Clues

Shown below is a table summarizing different findings on the peripheral blood smear findings and their associated conditions.

Findings on the peripheral blood smear	Associated conditions
Giant platelets	Hereditary thrombocytopenia
Schistocytes	DIC, TTP, HUS
Blasts	Bone marrow disorder
Dacrocytes	Myelofibrosis
Spherocytes RBC clumping	Evans syndrome
Nucleated RBCs	Hemolytic anemia, myelofibrosis, infiltration of the bone marrow
Lymphocytosis Neutrophilia Lymphocytosis Leukopenia Granulations	Infection
Macrocytosis Hypersegmented neutrophils	Megaloblastic anemia e.g. vitamin B12 deficiency, folate deficiency
Leukemic cells	Hematological malignancies
Pancytopenia	Aplastic anemia, myelodysplastic syndrome, leukemia
Microspherocytes	Evans syndrome, thrombotic angiopathies
Macrocytosis	Vitamin B12 deficiency, folate deficiency
Parasites	Malaria

Indications for Platelet Transfusion in Thrombocytopenia

Prophylactic Indications

• Consider platelet transfusion in the following conditions if the platelet count is less than:
  • 50,000/μL: Major surgery
  • 10,000/μL: Chemotherapy, bone marrow transplantation
  • 20,000/μL: Aggressive therapy for bladder tumors or demonstrable necrotic tumors
  • 10,000/μL: Treatment for acute leukemia
  • 20,000/μL: Before a lumbar puncture

• Bone marrow aspirations and biopsies can safely be performed at platelet counts <20,000/μL.

Therapeutic Indications

• Platelet transfusions in patients with chronic thrombocytopenia is usually indicated with a WHO bleeding grade of ≥ 2.
• For invasive procedures, it is recommended that a platelet count of at least 50,000/μL be maintained.
• The extent of surgery, ability to control bleeding, presence of platelet dysfunction and other coagulation defects determines when to make a decision to transfuse with a platelet count between 50,000 and 100,000/μL.
• Platelet transfusion to control or prevent bleeding with trauma or surgical procedures require higher transfusion thresholds of 100,000/μL for neurosurgical procedures.
• An acutely bleeding surgical patient usually requires platelet transfusion if the platelet count is < 50,000/μL and rarely if the count is > 100,000/μL.
• In acute DIC and with substantial bleeding, it is recommended to maintain the platelet count around 50,000/μL.
• In ITP, the transfusion of platelets is indicated in major and/or dangerous cases of hemorrhage (e.g. intracranial or intraocular hemorrhage).
• In acquired or congenital disorders of platelet function, platelet transfusion is indicated only in cases of perioperative hemorrhage.

WHO Bleeding Grades

Below is a table depicting the WHO bleeding grades for therapeutic platelet transfusion.

Grade 0	Grade 1 - Minor bleeding	Grade 2 - Mild bleeding	Grade 3 - Major bleeding	Grade 4 - Disabling bleeding
None	Petechiae Ecchymosis Occult blood in body secretions Mild vaginal spotting	Evidence of gross hemorrhage not requiring red cell transfusion e.g. Epistaxis, hematuria, hematemesis	Hemorrhage requiring transfusion of 1 or more units of red cells/day	Life threatening hemorrhage e.g. Intracranial hemorrhage, pericardial hemorrhage, pulmonary hemorrhage

Do's

• Order a peripheral blood smear in all patients with thrombocytopenia and check out the morphology of all blood cells lineages. The peripheral blood smear is one of the most important tests to order in the evaluation of thrombocytopenia.

• Consider the following diagnoses in the following categories of patients:
  • Critically ill patients: leukemia, manifested by blasts, and thrombotic microangiopathy, characterized by the presence of schistocytes
  • Hospitalized patients: HIT and DIC
  • Cardiac surgery patients: mechanical destruction, hemodilution, drug induced thrombocytopenia
  • Patients undergoing PCI: Drug induced thrombocytopenia (GpIIb-IIIa inhibitors)
  • Pregnant women: Gestational thrombocytopenia, preeclampsia, ITP

• If drug induced thrombocytopenia is suspected, stop the possible offending drug.

• Consider isolated thrombocytopenia in patients with thrombocytopenia in the absence of any systemic symptoms and the absence of any abnormalities in the other blood cells lineages.

• Order a bone marrow aspirate and biopsy in case of severe unexplained thrombocytopenia.