Lab It Up: Thrombocytopenia

Thrombocytopenia

Platelets <150,000 per mcL

Platelets are cells that aid in hemostasis at bleeding sites. They are primarily produced in the bone barrow and have an average life span of 7-10 days [1, 2].
The spleen normally stores 25% of the body’s platelets in reserves and can be released in times of adrenergic need [3].
Thrombocytopenia becomes more critical and often symptomatic when platelet counts are <50,000 per mcL [4].

Causes [4, 5]

Decreased platelet production

Bone marrow dysfunction such as:

Alcoholism
Chronic nutritional deficiencies, such as vitamin B12 and folate
Cirrhosis – from decreased thrombopoetin production in the liver
Viral infections, such as parvovirus B19, HIV, EBV, VZV, and CMV
Parasitic infections, such as Dengue and chikungunya
Sepsis
Aplastic anemia
Leukemia or another hematologic malignancy
Chemotherapy

Increased platelet destruction

Immune-mediated

Autoimmune disorders, such as immune thrombocytopenia (ITP)
Alloimmunity (post-transfusion)
Sepsis
Drug-induced
- Usually occurs 5-7 days after exposure to drug
- Heparin-induced thrombocytopenia (HIT) uniquely results in autoantibodies, which activate platelets to yield a high-risk hypercoagulable (venous>arterial thromboses) state. The incidence is 0.5-1% for those receiving unfractionated heparin (incidence is lower with low molecular weight heparin at 0.1-0.5%) [6].
- Perform a careful review of the patient’s medication list because a myriad of drugs can cause thrombocytopenia.

Mechanical destruction

Mechanical cardiac valve
Extracorporeal bypass

Increased platelet consumption

Microangiopathies (platelet deposition at endothelial injured sites) such as in thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS)
Disseminated intravascular coagulopathy (DIC)
Sepsis
Major trauma or surgery

Splenic sequestration

Hypersplenism can result in the sequestration of as much as 90% of the body’s platelets in the spleen [REF]. Causes may include:

Cirrhosis and portal hypertension
Congestive heart failure
Viral infections (mononucleosis, HIV)
Malarial infection
Lymphoma
Myeloproliferative disorders

Dilutional

Massive crystalloid fluid volume
Massive transfusion
Severe hemorrhage

Pseudothrombocytopenia

The in vitro clumping of platelets in the laboratory assay may result in a falsely low platelet count.
Re-test using non-EDTA anticoagulant in the blood tube.
No clinical significance

Special Populations

Pediatrics

Similar causes as for adults, but especially consider:

Immune thrombocytopenic purpura (ITP) [7]
- Can occur at any age, but usually occurs at age 2-5 years old
- Most common cause of acquired thrombocytopenia in children
Neonatal alloimmune thrombocytopenia [8]
- When maternal antibodies cross the placenta and attach to fetal platelet antigens from father

Pregnancy [9, 10]

The mean platelet count is slightly lower during pregnancy, with <1% of normal pregnancies reporting a platelet count <100,000/mcL. Physiologic thrombocytopenia may occur because of sequestration and pooling the splenic and placental circulation.

Gestational thrombocytopenia
- Occurs incidentally in 6% of pregnancies, usually near the time of delivery
- Typically fall in the range of 100,000-150,000/mcL.
Pregnancy-induced immune-mediated thrombocytopenia (ITP)
Eclampsia
- Typically occurs at 20+ weeks of gestation and can also occur post-partum
HELLP syndrome (hemolysis, elevated liver enzymes, low platelets)
- Typically occurs at 20+ weeks of gestation but can also occur post-partum

Key Insights

Obtain a blood smear

Peripheral blood smears may help to differentiate the cause for thrombocytopenia by looking at the platelet size/shape as well as evaluate the other 2 hematologic cells lines (red and white cells) [4].

Perform a careful investigation of the patient's medications

Drug-induced immune thrombocytopenia has been associated with over 300 medications. Investigate the patient’s medication list in the setting of thrombocytopenia [11].

Associated with COVID infection severity

COVID infection severity has been linked with thrombocytopenia through multiple mechanisms [12]:

Bone marrow suppression
Pulmonary microthrombi cause increased platelet destruction
Platelet autoantibody formation

COVID vaccine complication

Vaccine-induced immune thrombotic thrombocytopenia (VITT) can occurs with non-mRNA-based COVID-19 vaccines, such as from Astra Zeneca and Johnson & Johnson [13].

Similar to heparin-induced thrombocytopenia
- Similar pathophysiology being immune-mediated)
- Hypercoagulable state
- Occurs 5-10 days after COVID vaccine
Increased platelet consumption

Lab It Up Library

You order a battery of laboratory tests on your patient in the Emergency Department and few results are highlighted as abnormal in red. Why is it abnormal? Are you forgetting causes? The “Lab It Up” library helps Emergency Department clinicians to recall relevant differential diagnoses for abnormal laboratory results.

View the full indexed list in this series.

Lab It Up Library

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Originally published Feb 16, 2023

References

Harker LA, Roskos LK, Marzec UM, et al. Effects of megakaryocyte growth and development factor on platelet production, platelet life span, and platelet function in healthy human volunteers. Blood. 2000;95(8):2514-2522. PMID 10753829
Arnold DM, Lim W. A rational approach to the diagnosis and management of thrombocytopenia in the hospitalized patient. Semin Hematol. 2011;48(4):251-258. doi:10.1053/j.seminhematol.2011.08.002. PMID 22000090
Kapila V, Wehrle CJ, Tuma F. Physiology, Spleen. [Updated 2022 May 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.
Gauer RL, Braun MM. Thrombocytopenia. Am Fam Physician. 2012;85(6):612-622. PMID 22534274 (excellent review, open access)
Swain F, Bird R. How I approach new onset thrombocytopenia. Platelets. 2020;31(3):285-290. doi: 10.1080/09537104.2019.1637835. Epub 2019 Jul 3. PMID: 31269407. PMID 31269407
Arepally GM, Cines DB. Pathogenesis of heparin-induced thrombocytopenia. Transl Res. 2020;225:131-140. doi:10.1016/j.trsl.2020.04.014. PMID 32417430[Open access full article]
Neunert C, Terrell DR, Arnold DM, et al. American Society of Hematology 2019 guidelines for immune thrombocytopenia [published correction appears in Blood Adv. 2020 Jan 28;4(2):252]. Blood Adv. 2019;3(23):3829-3866. doi:10.1182/bloodadvances.2019000966
Norton T, Newberry D, Jnah A. Neonatal Alloimmune Thrombocytopenia: A Concise Review. Adv Neonatal Care. 2021;21(2):115-121. doi:10.1097/ANC.0000000000000775. PMID 32657948
Reese JA, Peck JD, Deschamps DR, et al. Platelet Counts during Pregnancy. N Engl J Med. 2018;379(1):32-43. doi:10.1056/NEJMoa1802897. PMID 29972751
Burrows RF, Kelton JG. Incidentally detected thrombocytopenia in healthy mothers and their infants. N Engl J Med. 1988;319(3):142-145. doi:10.1056/NEJM198807213190304. PMID 3386694
Bakchoul T, Marini I. Drug-associated thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2018;2018(1):576-583. doi:10.1182/asheducation-2018.1.576. PMID 30504360
Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020;506:145-148. doi:10.1016/j.cca.2020.03.022. PMID 32178975
Aleem A, Nadeem AJ. Coronavirus (COVID-19) Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT) [Updated 2022 Oct 3]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.