What are the potential causes of a patient presenting with low hematocrit (Hct) and low platelet count?

Causes of Low Hematocrit and Low Platelet Count

The combination of low hematocrit and low platelet count most commonly results from bone marrow failure syndromes, consumptive coagulopathies (particularly DIC), thrombotic microangiopathies (especially TTP), or acute hemorrhage with dilutional effects from resuscitation. 1, 2

Primary Diagnostic Categories

Bone Marrow Failure/Production Disorders

• Myelodysplastic syndromes and acute leukemias directly impair both red cell and platelet production through disrupted megakaryocyte function and erythropoiesis, requiring bone marrow examination for definitive diagnosis 1
• Aplastic anemia causes pancytopenia through complete marrow failure, presenting with sustained severe thrombocytopenia alongside anemia 1
• Myelofibrosis disrupts normal marrow architecture, reducing effective production of both cell lines 3, 1
• Bone marrow infiltration by malignancies (lymphoma, metastatic solid tumors) replaces normal hematopoietic tissue 1

Consumptive/Destructive Processes

• Disseminated intravascular coagulation (DIC) causes simultaneous consumption of platelets and coagulation factors with microangiopathic hemolysis, characterized by prolonged PT/aPTT, low fibrinogen, and elevated D-dimers 3, 1
• Thrombotic thrombocytopenic purpura (TTP) produces thrombocytopenia with microangiopathic hemolytic anemia (low hematocrit from hemolysis), requiring urgent plasma exchange 3, 1
• Heparin-induced thrombocytopenia (HIT) typically causes moderate thrombocytopenia (30-70 G/L) occurring 5-10 days after heparin exposure, though anemia is not a primary feature unless complicated by thrombosis or bleeding 3, 1

Hemorrhage-Related Causes

• Acute hemorrhage with resuscitation produces both low hematocrit from blood loss and low platelets from consumption and dilution with crystalloid/colloid fluids 3, 4
• A hematocrit drop ≥6.5% within 15-30 minutes has high specificity (0.93-1.0) for serious bleeding in trauma, while platelet consumption occurs simultaneously 4
• Resuscitation fluids cause hemodilution that artificially lowers both hematocrit and platelet counts independent of actual blood loss 3, 4

Hypersplenism/Sequestration

• Hepatic disease with portal hypertension causes splenic sequestration of both red cells and platelets, combined with decreased thrombopoietin production 2, 5
• Splenomegaly from any cause (lymphoma, storage diseases, portal hypertension) sequesters 30-90% of the platelet mass and increases red cell destruction 5

Special Population: Cyanotic Congenital Heart Disease

• Polycythemia with hyperviscosity paradoxically triggers platelet consumption through DIC-like mechanisms, with platelet counts inversely correlating with hematocrit levels 3, 1
• Platelet survival decreases to <80 hours (normal 80-130 hours) with increased fibrinolysis evidenced by elevated D-dimers 3, 1
• Iron deficiency develops from chronic phlebotomy attempts to reduce polycythemia, causing microcytic anemia despite elevated hematocrit initially 3

Critical Diagnostic Algorithm

Step 1: Exclude Pseudothrombocytopenia

• Always examine peripheral blood smear to exclude EDTA-dependent platelet clumping, which occurs in 0.1% of adults 1, 2
• Repeat platelet count in heparin or citrate tube if clumping suspected 1, 2

Step 2: Assess Acuity and Severity

• Acute presentation (<72 hours) suggests hemorrhage, DIC, TTP, HIT, or drug-induced causes requiring immediate intervention 2, 5, 6
• Chronic presentation suggests bone marrow disorders, hypersplenism, or chronic liver disease 2, 5

Step 3: Identify Life-Threatening Causes First

• Check for microangiopathic hemolytic anemia (schistocytes on smear, elevated LDH, low haptoglobin) indicating TTP or DIC 1, 2
• Calculate 4T score if heparin exposure within 3 months; scores ≥6 indicate high HIT probability requiring immediate anti-PF4 antibody testing 3, 1
• Assess for DIC with PT/aPTT, fibrinogen, and D-dimers; prolonged PT/aPTT with low fibrinogen and elevated D-dimers confirms diagnosis 3, 1

Step 4: Evaluate for Hemorrhage

• Serial hematocrit measurements at 15 minutes, 30 minutes, then every 4-6 hours; any decline ≥6.5% in first 15-30 minutes warrants heightened concern for active bleeding 4
• **Initial hematocrit <35%** is an independent risk factor for severe bleeding, and a drop >20% within 24 hours defines severe hemorrhage 4
• A normal initial hematocrit does not exclude active bleeding due to physiological fluid shifts and hemodilution from resuscitation 4

Step 5: Bone Marrow Examination When Indicated

• Perform bone marrow biopsy when peripheral smear shows abnormal cells, pancytopenia is present, or no clear consumptive/destructive cause is identified 1, 2
• Bone marrow examination distinguishes production disorders (MDS, leukemia, aplastic anemia, myelofibrosis) from peripheral destruction 1

Common Pitfalls to Avoid

• Never rely on single hematocrit measurement as isolated marker for bleeding; normal admission hematocrit does not preclude significant injury 4
• Missing drug-induced thrombocytopenia by failing to obtain comprehensive medication history including over-the-counter drugs, herbal supplements, and recent antibiotics 1, 2
• Overlooking HIT in patients receiving any heparin exposure (including heparin flushes), particularly when thrombosis accompanies thrombocytopenia rather than bleeding 3, 1
• Failing to recognize antiphospholipid syndrome, which causes thrombocytopenia associated with thrombosis rather than bleeding, distinguishing it from typical immune thrombocytopenia 3, 1
• Underestimating coagulopathy in hypothermic patients because laboratories re-warm samples to 37°C before testing, masking the true severity of platelet and coagulation dysfunction 3
• Missing post-transfusion purpura from alloimmunization, which causes sudden major thrombocytopenia with hemorrhagic complications requiring specific treatment 3, 1

Immediate Management Considerations

• Platelet transfusion recommended when active hemorrhage present or platelet counts <10 × 10³/μL, in addition to treating underlying cause 2
• Avoid platelet transfusion in TTP as it may worsen thrombosis; urgent plasma exchange is definitive treatment 1
• Stop all heparin immediately if 4T score ≥4 and initiate alternative anticoagulation while awaiting anti-PF4 antibody results 3
• Correct hypothermia, acidosis, and hypocalcemia in trauma/hemorrhage patients as these profoundly impair both platelet function and coagulation enzyme activity 3