Causes of Low Platelets (Thrombocytopenia)
Low platelet counts result from four primary mechanisms: decreased production, increased destruction, splenic sequestration, or dilution, with immune thrombocytopenia (ITP) and drug-induced thrombocytopenia being the most common causes in otherwise healthy patients with isolated thrombocytopenia. 1
Primary Mechanisms and Causes
Decreased Platelet Production
- Bone marrow infiltration from acute leukemia, lymphoma, or metastatic solid tumors 2
- Myelodysplastic syndrome causing ineffective platelet production 2
- Bone marrow failure from aplastic anemia or chemotherapy-induced suppression 3
- Nutritional deficiencies, particularly vitamin B12 or folate deficiency 3
Increased Platelet Destruction
Immune-mediated destruction:
- Primary immune thrombocytopenia (ITP) - autoimmune destruction with platelet counts typically <100 × 10⁹/L in the absence of other identifiable causes 4, 1
- Secondary ITP associated with systemic lupus erythematosus, other autoimmune diseases, viral infections (HIV, hepatitis C), and Helicobacter pylori infection 4, 1
- Drug-induced thrombocytopenia from medications including heparin, antibiotics (especially beta-lactams, sulfonamides, vancomycin), anticonvulsants, diuretics, and chemotherapy agents 1, 5
- Heparin-induced thrombocytopenia (HIT) - a prothrombotic condition with thrombocytopenia typically occurring 5-10 days after heparin initiation, with platelet counts usually between 30-70 × 10⁹/L and rarely below 20 × 10⁹/L 1
Non-immune destruction:
- Thrombotic microangiopathies including thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) 5, 2
- Disseminated intravascular coagulation (DIC) from sepsis, malignancy, or obstetric complications 3, 6
- HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) in pregnancy 5
Splenic Sequestration
- Portal hypertension and cirrhosis causing splenomegaly with platelet sequestration 1
- Splenic enlargement from any cause can trap up to 90% of circulating platelets 3
Dilutional Thrombocytopenia
- Massive transfusion or fluid resuscitation diluting platelet concentration 3
Pregnancy-Related
- Gestational thrombocytopenia (most common cause in pregnancy, typically mild) 1, 3
- Preeclampsia/eclampsia and HELLP syndrome 5
Diagnostic Approach
Initial Evaluation
First, exclude pseudothrombocytopenia by collecting blood in a tube containing heparin or sodium citrate and repeating the platelet count 5. This laboratory artifact occurs in approximately 0.1% of cases due to EDTA-dependent platelet clumping 1.
Obtain a complete blood count with differential to identify isolated thrombocytopenia versus other cytopenias (which suggests bone marrow failure or infiltration) 1, 5.
Examine the peripheral blood smear to assess platelet size, identify schistocytes (suggesting TTP/HUS), evaluate red and white cell morphology, and confirm true thrombocytopenia 1, 5. Key smear findings in ITP include normal to large platelets, normal red cell morphology, and normal white cell morphology 1.
Distinguishing Acute from Chronic
Review previous platelet counts to distinguish acute from chronic thrombocytopenia 5. An abrupt decrease within 1-2 days after an initial increase approximately 1-2 weeks after surgery strongly suggests immunologic causes, including HIT, other drug-induced immune thrombocytopenia, or posttransfusion purpura 6.
When to Suspect Specific Causes
Suspect HIT when: Platelet count drops by ≥50% from baseline 5-10 days after heparin exposure, or within 24 hours if recent heparin exposure (within 100 days) 1, 5. Stop all heparin immediately and initiate alternative anticoagulation with a non-heparin agent 1.
Suspect TTP/HUS when: Thrombocytopenia is accompanied by microangiopathic hemolytic anemia (schistocytes on smear), elevated LDH, and renal dysfunction 5, 2. These patients require emergency hospitalization 5.
Suspect ITP when: Isolated thrombocytopenia in the absence of systemic illness, with normal or large platelets on smear 1, 5, 7.
Bone Marrow Examination
Bone marrow examination is unnecessary in children and adolescents with typical features of ITP 4. In adults, bone marrow biopsy should be considered when there are atypical features suggesting bone marrow infiltration or myelodysplastic syndrome 2.
Clinical Significance and Bleeding Risk
Bleeding risk correlates with platelet count: 1
- >50 × 10⁹/L: Generally asymptomatic 5
- 20-50 × 10⁹/L: Mild skin manifestations (petechiae, purpura, ecchymosis) 5
- <10 × 10⁹/L: High risk of serious bleeding 1, 5
Important caveat: Certain conditions cause both bleeding and thrombosis despite low platelet counts, including antiphospholipid syndrome, HIT, and thrombotic microangiopathies 5. In these conditions, platelet transfusion may be contraindicated and worsen thrombosis.
Treatment Principles
Platelet Transfusion Indications
Transfuse platelets for: 1
- Active hemorrhage regardless of platelet count
- Platelet count <10 × 10⁹/L even without bleeding
- Before high-risk procedures when platelets <50 × 10⁹/L
Important limitation: In liver disease, prophylactic platelet transfusions to prevent procedural bleeding lack evidence of benefit and carry transfusion-related risks 1.
ITP-Specific Treatment
For children with no bleeding or mild bleeding (skin manifestations only), manage with observation alone regardless of platelet count 4, 1. This is a strong recommendation as most pediatric ITP resolves spontaneously.
For pediatric patients requiring treatment, use a single dose of IVIg (0.8-1 g/kg) or a short course of corticosteroids as first-line treatment 4, 1. IVIg can be used if a more rapid increase in platelet count is desired 4.
For adults with ITP requiring treatment: Corticosteroids, IVIg, or anti-RhD immunoglobulin are classical initial treatments 7. However, these agents generally cannot induce long-term response in most patients 7.
Second-line options for refractory ITP include: 1, 7
- Thrombopoietin receptor agonists (romiplostim, eltrombopag)
- Rituximab
- Fostamatinib
- Splenectomy (delayed for at least 12 months unless severe disease) 4
For lupus-associated thrombocytopenia (platelet count <30,000/mm³): Moderate/high doses of corticosteroids in combination with immunosuppressive agents (azathioprine, mycophenolate mofetil, or cyclosporine) 4. Initial therapy with pulses of intravenous methylprednisolone (1-3 days) is encouraged 4. Rituximab should be considered in patients with no response to corticosteroids or relapses 4.
Drug-Induced Thrombocytopenia
Discontinue the offending agent immediately 1. This is the most critical intervention, as platelet counts typically recover within 7-10 days after drug discontinuation 5.