Thrombocytopenia – an ED Approach

Alex Koo, MD

Thrombocytopenia is defined by a platelet count less than 150,000 platelets/microliter in adults.  Subcategorized, thrombocytopenia can be broken down into mild, moderate, and severe:

Mild – 100,000 to 149,000/microL

Moderate – 50,000 to 99,000/microL

Severe – <50,000/microL

Thrombocytopenias have a large etiology broken down into three subcategories:

1. Decreased production: Viral, Drugs, Aplastic anemia, Nutrient Deficiencies (i.e. folate, B12), Chronic alcohol use, malignancy
2. Increased destruction: Heparin Induced Thrombocytopenia (HIT), Idiopathic, Autoimmune
3. Sequestration: Hypersplenism, Pregnancy

Patient History

In taking a history and physical, it’s important to determine if the patient has any history suggestive of bleeding as petechiae, gingival bleeding, or easy bruising.  Also, any signs of infection that could contribute to a drop in platelet count can be explored.  Relevant family history of thrombocytopenia or bleeding disorders and recent new medications should be reviewed.  Medications commonly associated with thrombocytopenia are NSAIDs, acetaminophen, trimethoprim-sulfate, and quinine-based products.¹  Lastly, comparing current platelet counts to previous platelet counts may be useful. 

A cachectic patient with hypermetabolic metastatic lung cancer may chronically have platelet counts of 60,000/microL and may not be contributory to their emergency department visit.  However, a patient with a fever and body aches returning from Nigeria with a platelet count drop from 400,000 to 200,000/microL may be relevant.  

Thrombocytopenia Workup

Thrombocytopenia must be taken in the context of the patient’s whole clinical picture.  In the emergency department, the exact etiology of a patient may not always be elucidated.  However, there are dangerous diagnoses to consider and example further bloodwork may be considered:

Complete Blood Count

Comprehensive Metabolic Panel: liver function testing with bilirubin, creatinine

“Hemolysis labs”: Peripheral smear, lactate dehydrogenase, haptoglobin, Coombs’ testing

Urinalysis: Proteinuria

DIC Labs: Fibrinogen, D-dimer, PT/INR, PTT

Stool for Shiga Toxin enzyme immunoassay or polymerase chain reaction

Diagnoses

Idiopathic (Immune) Thrombocytopenic Purpura (ITP)^2,3

1. A combination of decreased production with T and B cell-mediated platelet destruction
2. Occurs in 2 forms:
   1. Children < 10 years
      1. Typically acute and self-limited
   2. Adults
      1. More commonly chronic
3. Treatment:
   1. Steroids, IV Immunoglobulin
   2. Splenectomy, if severe and unremitting
   3. Platelets can be given in acute situation with concern for active bleeding, but will be destroyed
   4. RhoGAM (decreases macrophage activity), Rituximab (Chemotherapy), or Eltrombopag (Thrombopoietin stimulator)

Thrombotic Thrombocytopenic Purpura (TTP)⁴

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1. ADAMTS13, an enzyme,  usually cleaves von Willebrand Factor (vWF) multimers into monomers.  However, in TTP, ADAMTS13 is either not working or has decreased in amount.  This leads to long chains of vWF that can obstruct microvessels, leading to manifestation of disease.
2. “FAT RN” mnemonic– Fever, Anemia, Thrombocytopenia, Renal Failure, Neurological symptoms (i.e. confusion, neurological focal deficits)
3. Treatment:
   1. NO platelets as this can lead to worsening disease
   2. Plasmapheresis to remove vWF multimer chains
   3. Steroids
   4. Fresh Frozen Plasma: Repletes ADAMTS13

Hemolytic Uremic Syndrome (HUS)⁵

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1. HUS is characterized by inappropriate complement activation that can be set off by autoantibodies and infection.  In typical HUS, Shiga toxin–producing Escherichia coli (STEC) infection activates these complements (85% of cases), but HUS can occur with triggers of autoantibodies due to other causes as cancer, transplantation, pregnancy, and certain drugs..
2. Triad: Anemia, Thrombocytopenia, and Acute Kidney Failure
3. Treatment:
   1. NO platelets and NO antibiotics in typical HUS as this can worsen release of Shiga toxin
   2. Determining any secondary cause and treating such
   3. Severe cases of CNS involvement can be treated with Eculizumab

Heparin-Induced Thrombocytopenia (HIT)⁶

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1. Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin.5
2. Characterized by the 4 T’s:
   1. Thrombocytopenia: Drop > 50% baseline
   2. Time: 4-14 days from heparin exposure
   3. Thrombosis: DVT, PE, Skin necrosis
   4. No oTher cause 
3. Treatment:
   1. Discontinuation of all heparin-based products
   2. Intravenous direct thrombin inhibitor (i.e. argatroban, bivalirudin)

Disseminated Intravascular Coagulopathy (DIC)⁷

1. Widespread microvascular thrombosis and consumption of clotting factors/platelets, commonly in a massive systemic inflammatory response.  There ends up being an imbalance in coagulation and bleeding.
2. Patients experiencing DIC may experience inappropriate bleeding from multiple sites as gingiva, urinary catheters, mucosal surfaces and inappropriate coagulation as pulmonary emboli, ischemic strokes, and acute coronary syndrome.
3. Treatment:
   1. Treat underlying cause (i.e. sepsis source)
   2. Support with FFP, cryoprecipitate, platelets

HELLP Syndrome⁸

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1. Hemolysis with elevated liver enzymes and low platelet count
2. Systemic inflammatory disorder in pregnant and postpartum patients with inappropriate complement activation.
3. Defined by:
   1. Hemolysis as defined by 2 of the following: schistocytes and/or Burr cells on smear, serum bilirubin > 1.2 mg/dL, low haptoglobin or high LDH, and/or low hemoglobin. 
   2. Elevated liver enzymes of ALT or AST greater than 2 times the upper limit normal
   3. Low platelets less than 100,000 cells/microL

References

1. Lambert MP, Gernsheimer TB. Clinical updates in adult immune thrombocytopenia. Blood. 2017 May 25;129(21):2829-2835. doi: 10.1182/blood-2017-03-754119. Epub 2017 Apr 17. PMID: 28416506; PMCID: PMC5813736.
2. Faki Osman ME. Childhood immune thrombocytopenia: Clinical presentation and management. Sudan J Paediatr. 2012;12(1):27-39. PMID: 27493327; PMCID: PMC4949815.
3. Bakchoul T, Marini I. Drug-associated thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2018 Nov 30;2018(1):576-583. doi: 10.1182/asheducation-2018.1.576. PMID: 30504360; PMCID: PMC6246020.
4. Long B, Bridwell RE, Manchanda S, Gottlieb M. Evaluation and Management of Thrombotic Thrombocytopenic Purpura in the Emergency Department. J Emerg Med. 2021 Dec;61(6):674-682. doi: 10.1016/j.jemermed.2021.07.045. Epub 2021 Sep 10. PMID: 34518045.
5. Jokiranta TS. HUS and atypical HUS. Blood. 2017 May 25;129(21):2847-2856. doi: 10.1182/blood-2016-11-709865. Epub 2017 Apr 17. PMID: 28416508; PMCID: PMC5445567.
6. Arepally GM. Heparin-induced thrombocytopenia. Blood. 2017 May 25;129(21):2864-2872. doi: 10.1182/blood-2016-11-709873. Epub 2017 Apr 17. PMID: 28416511; PMCID: PMC5445568.
7. Costello RA, Leslie SW, Nehring SM. Disseminated Intravascular Coagulation. [Updated 2024 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK441834
8. Khalid F, Mahendraker N, Tonismae T. HELLP Syndrome. [Updated 2023 Jul 29]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK560615/