Thrombocytopenia Causes

Aka: Thrombocytopenia Causes, Low Platelet Causes

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II. Causes: Emergent Thrombocytopenia

  1. Heparin Induced Thrombocytopenia (HIT)
  2. Thrombotic Thrombocytopenic Purpura (TTP)
  3. Hemolytic Uremic Syndrome (HUS)
  4. Preeclampsia with HELLP Syndrome

III. Causes: Common by Severity

  1. Factitious Thrombocytopenia
    1. Pseudothrombocytopenia
  2. Mild to moderate Thrombocytopenia
    1. Alcohol Abuse
    2. Congenital Thrombocytopenia
    3. Gestational Thrombocytopenia
    4. Heparin Induced Thrombocytopenia
    5. Preeclampsia with HELLP Syndrome
    6. Viral Infections (e.g. CMV, EBV, VZV, HIV, Hepatitis C, Parvovirus B19)
    7. Tick Borne Illness (Anaplasmosis, Babesiosis, Rocky Mountain Spotted Fever, Lyme Disease)
  3. Moderate to severe Thrombocytopenia
    1. Bone Marrow suppression by Chemotherapy or radiation
    2. Bone Marrow infiltration by malignancy
    3. Disseminated Intravascular Coagulation
    4. Drug induced Thrombocytopenia
    5. Immune Thrombocytopenic Purpura
    6. Thrombotic Thrombocytopenic Purpura or Hemolytic Uremic Syndrome

IV. Causes: Common by Timing

  1. Acute
    1. Bone Marrow suppression by Chemotherapy or radiation
    2. Bone Marrow infiltration by malignancy
    3. Viral Infections (e.g. CMV, EBV, VZV, HIV, HCV, Parvovirus B19)
    4. Acute Leukemia
    5. Aplastic Anemia
    6. Drug-Induced Thrombocytopenia
    7. Preeclampsia with HELLP Syndrome
    8. Heparin Induced Thrombocytopenia
    9. Thrombotic Thrombocytopenic Purpura or Hemolytic Uremic Syndrome
  2. Chronic
    1. Alcohol Abuse
    2. Congenital Disorders (see hereditary decreased Platelet disorders below)
    3. Immune Thrombocytopenic Purpura
    4. Cirrhosis or other chronic liver disorder
    5. Myelodysplastic Syndrome

V. Causes: Children

  1. Neonatal causes
    1. Sepsis
    2. Neonatal Respiratory Distress Syndrome (RDS)
    3. Maternal Pregnancy Induced Hypertension
    4. Alloimmune Thrombocytopenia (maternal antibodies cross placenta)
      1. Presents in first 48 hours of life
      2. High risk of Intracranial Hemorrhage
    5. Necrotizing Enterocolitis
    6. Immune Thrombocytopenic Purpura
    7. Genetic Syndromes (uncommon)
    8. Congenital Leukemia
    9. TORCH Infections
    10. Nonaccidental Trauma
  2. Childhood causes
    1. Immune Thrombocytopenic Purpura (common)
    2. Drug-Induced Thrombocytopenia (common)
    3. Cancer involving Bone Marrow (e.g. Leukemia)
    4. Thrombotic Thrombocytopenic Purpura or Hemolytic Uremic Syndrome
    5. Von Willebrand Disease Type II
    6. Autoimmune Disease
    7. Fanconi Anemia
    8. Immunizations (MMR Vaccine, Varicella Vaccine, H1N1 Influenza Vaccine)

VI. Causes: Pregnancy

  1. Preeclampsia with HELLP Syndrome
  2. Acute Fatty Liver of Pregnancy
    1. Rare third trimester disorder presenting with Abdominal Pain, Nausea, Vomiting and Altered Mental Status
  3. Gestational Thrombocytopenia
    1. Benign condition in second half of pregnancy
    2. Accounts for 80% of Thrombocytopenia in pregnancy (Platelet Count >80k)
    3. Distinguish from mild immune Thrombocytopenia

VII. Causes: Platelet Destruction of Consumption

  1. Immune-Mediated
    1. Drug induced Thrombocytopenia
    2. Heparin-Induced Thrombocytopenia
    3. Idiopathic Thrombocytopenic Purpura (ITP)
    4. Post-Transfusion (within 5 to 14 days)
    5. Vasculitis
    6. Autoimmune Hemolytic Anemia
    7. Chronic Lymphocytic Leukemia (CLL)
    8. Antiphospholipid Syndrome
    9. Systemic Lupus Erythematosus (SLE) in 10% of cases
    10. Inflammatory Bowel Disease
    11. Rheumatoid Arthritis
    12. Evans Syndrome
    13. Sarcoidosis
    14. Hodgkin Lymphoma
    15. Chronic Lymphocytic Leukemia
    16. Human Immunodeficiency Virus (HIV)
    17. Cytomegalovirus (CMV)
    18. Herpes Virus infection
  2. Immune-Mediated in Newborns
    1. Fetal - maternal ABO Incompatibility
    2. Neonatal isoimmune or alloimmune Thrombocytopenia
      1. Maternal Antibody to fetal PlateletAntigen (P1)
    3. Neonatal autoimmune Thrombocytopenia
      1. Maternal Antibody binds fetal Platelets
      2. Maternal conditions
        1. Idiopathic Thrombocytopenic Purpura
        2. Systemic Lupus Erythematosus
        3. Drug induced Thrombocytopenia
  3. Non-immune Mediated
    1. Preeclampsia (HELLP Syndrome)
    2. Prosthetic Heart Valves (e.g. aortic Valve Replacement)
    3. Thrombotic Thrombocytopenic Purpura (TTP)
    4. Sepsis
    5. Disseminated Intravascular Coagulation (DIC)
    6. Hemolytic Uremic Syndrome (HUS)
    7. Hemorrhage with extensive transfusion

VIII. Causes: Decreased Platelet Production

  1. Acquired
    1. Infiltrative process
      1. Leukemia
      2. Histiocytosis
      3. Lymphoma
      4. Myelodysplastic Syndrome
      5. Myelofibrosis
      6. Storage disease
      7. Neuroblastoma
      8. Granulomatosis
      9. Osteopetrosis
    2. Suppression of Megakaryocytes (or Bone Marrow failure)
      1. Alcohol Abuse
      2. Radiation
      3. Infection
        1. Fetal TORCH Virus infection
        2. Cytomegalovirus
        3. Epstein-Barr Virus (Mononucleosis)
        4. Varicella Zoster Virus
        5. Hepatitis C virus
        6. HIV Infection
        7. Parvovirus B19
        8. Rickettsia (includes Rocky Mountain Spotted Fever)
      4. Tick Borne Illness
        1. Rocky Mountain Spotted Fever
        2. Anaplasmosis
        3. Ehrlichiosis
        4. Babesiosis
        5. Colorado Tick Fever
      5. Paroxysmal Nocturnal Hemoglobinuria
      6. Scwachman-Diamond Syndrome
      7. Aplastic Anemia
      8. Medications
        1. See Drug induced Thrombocytopenia
        2. Alkylating Agents
        3. Antimetabolites
        4. Anticonvulsants
        5. Hydrochlorothiazide or other Thiazide Diuretics
        6. Estrogen
  2. Hereditary
    1. Alport Syndrome
    2. Bernard-Soulier Syndrome
    3. Thrombocytopenia-absent radii (TAR syndrome)
      1. Autosomal Recessive trait
      2. Purpura immediately or within weeks of birth
    4. Fanconi Anemia
    5. Wiskott-Aldrich syndrome (x-linked condition)
      1. Decreased Platelets (Microthrombocytopenia)
        1. Adequate Megakaryocytes in Bone Marrow
      2. Eczematous Dermatitis
      3. Repeated infection (Immunodeficiency)
    6. May-Hegglin anomaly
      1. Increased Megakaryocytes
      2. Ineffective thrombopoiesis
    7. Congenital amegakaryocytic Thrombocytopenia
      1. Rare isolated newborn Thrombocytopenia

IX. Causes: Platelet sequestration and miscellaneous causes

  1. Alcohol Abuse
  2. Splenomegaly or hypersplenism
  3. Cavernous Hemangioma
  4. Pseudothrombocytopenia
  5. Dilutional Thrombocytopenia (e.g. excessive fluid Resuscitation)
  6. Gestational Thrombocytopenia
  7. Chronic Liver Disease (e.g. Cirrhosis)
  8. Pulmonary Embolism
  9. Pulmonary Hypertension

X. References

  1. Holland (2016) Thrombocytopenia in Children Lecture, ACEP PEM Conference, Orlando, attended 3/9/2016
  2. Gauer (2012) Am Fam Physician 85(6): 612-22 [PubMed]
  3. Gauer (2022) Am Fam Physician 106(3): 288-98 [PubMed]
  4. George (2000) Lancet 355(9214):1531-9 [PubMed]
  5. Goldstein (1996) Am Fam Physician 53(3):915-20 [PubMed]
  6. Rizvi (1999) Curr Opin Hematol 6(5):349-53 [PubMed]

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