What can cause anemia and thrombocytopenia in adults?

Causes of Anemia and Thrombocytopenia in Adults

The combination of anemia and thrombocytopenia in adults most commonly results from bone marrow disorders (myelodysplastic syndromes, leukemias, aplastic anemia), systemic infections (HIV, HCV), autoimmune conditions (systemic lupus erythematosus), medications causing bone marrow suppression, or thrombotic microangiopathies (TTP-HUS, DIC). 1

Primary Diagnostic Categories

Bone Marrow Failure or Infiltration

• Myelodysplastic syndromes, leukemias, and other malignancies impair both megakaryocyte function and erythropoiesis, causing concurrent cytopenias that require bone marrow examination in patients over 60 years or those with systemic symptoms 1, 2
• Aplastic anemia and megaloblastic anemia produce pancytopenia through bone marrow failure mechanisms 1
• Bone marrow fibrosis disrupts normal hematopoiesis, leading to both anemia and thrombocytopenia 1

Autoimmune and Inflammatory Disorders

• Systemic lupus erythematosus (SLE) causes secondary immune thrombocytopenia with concurrent anemia of chronic disease, often presenting with constitutional symptoms, hepatomegaly, or lymphadenopathy 1, 3
• Other autoimmune/immunodeficiency disorders including common variable immune deficiency can present with both cytopenias 1, 3

Infectious Causes

• HIV and hepatitis C virus (HCV) infections produce thrombocytopenia clinically indistinguishable from primary ITP while simultaneously causing anemia through chronic inflammation and bone marrow suppression 1, 3, 4
• Parvovirus B19 infection causes pure red cell aplasia with anemia, which may coexist with thrombocytopenia 1
• Cytomegalovirus (CMV) infection presents with both anemia and thrombocytopenia 1

Medication-Induced Cytopenias

• Azathioprine and mycophenolate mofetil are myelosuppressive immunosuppressants that cause anemia frequently associated with leukopenia and/or thrombocytopenia 1
• Sirolimus demonstrates dose-dependent association with anemia and may cause thrombotic microangiopathy with thrombocytopenia 1
• Ganciclovir and trimethoprim-sulfamethoxazole commonly cause both anemia and thrombocytopenia 1
• Drug-induced thrombocytopenia from prescription or non-prescription medications, alcohol abuse, or quinine consumption can occur alongside anemia from the same agents 1

Thrombotic Microangiopathies

• Thrombotic thrombocytopenic purpura–hemolytic uremic syndrome (TTP-HUS) produces schistocytes on peripheral smear, indicating microangiopathic hemolytic anemia with concurrent thrombocytopenia 1
• Disseminated intravascular coagulation (DIC) causes consumptive coagulopathy with both anemia from hemolysis and thrombocytopenia from platelet consumption 3, 5
• Antiphospholipid syndrome can cause thrombotic microangiopathy leading to both cytopenias 3

Liver Disease and Hypersplenism

• Alcoholic liver cirrhosis causes hypersplenism with splenic sequestration of platelets while producing anemia through multiple mechanisms including nutritional deficiencies, bone marrow suppression, and bleeding 1, 2
• Portal hypertension from advanced liver fibrosis causes platelet trapping and contributes to thrombocytopenia in up to 76% of patients with chronic liver disease 2

Nutritional Deficiencies

• Iron deficiency uncommonly causes thrombocytopenia (iron deficiency-associated thrombocytopenia, IDAT) alongside anemia, often misdiagnosed as ITP, with median platelet counts around 30.5 × 10⁹/L 6
• Megaloblastic anemia from folate or vitamin B12 deficiency can present with thrombocytopenia due to ineffective thrombopoiesis 1

Lymphoproliferative Disorders

• Chronic lymphocytic leukemia (CLL) causes secondary ITP with thrombocytopenia while producing anemia through bone marrow infiltration or autoimmune hemolysis 1
• Other lymphoproliferative disorders infiltrate bone marrow, causing both cytopenias 1, 3

Essential Diagnostic Approach

Initial Laboratory Evaluation

• Complete blood count with differential distinguishes isolated dual cytopenias from pancytopenia, which strongly suggests bone marrow failure or infiltration 3, 2
• Peripheral blood smear examination by a qualified hematologist or pathologist is paramount, identifying schistocytes (TTP-HUS), leukocyte inclusion bodies (MYH9-related disease), or abnormal white cells suggesting malignancy 1, 3
• Reticulocyte count determines whether anemia results from poor production or increased destruction of red blood cells 1

Critical Red Flags Requiring Immediate Investigation

• Moderate or massive splenomegaly suggests alternative causes beyond primary ITP, including lymphoproliferative disorders or portal hypertension 1
• Constitutional symptoms (fever, weight loss), hepatomegaly, or lymphadenopathy indicate underlying disorders such as HIV, SLE, or lymphoproliferative disease 1, 3
• Schistocytes on peripheral smear indicate thrombotic microangiopathy requiring urgent evaluation for TTP-HUS or DIC 1

Mandatory Infectious Disease Screening

• HIV and HCV serologic testing should be performed routinely in all adult patients with suspected ITP regardless of local prevalence or documented risk factors, as these infections can occur years before other symptoms develop 1, 3, 2
• Helicobacter pylori testing using urea breath test or stool antigen test should be considered, as eradication therapy can resolve thrombocytopenia 1, 3

When Bone Marrow Examination Is Indicated

• Age greater than 60 years mandates bone marrow examination to exclude myelodysplastic syndromes, leukemias, or other malignancies 1, 3, 2
• Systemic symptoms or abnormal signs require both bone marrow aspirate and biopsy with flow cytometry and cytogenetic testing 1, 3
• Anemia disproportionate to bleeding or abnormal hemoglobin, white blood cell count, or white cell morphology necessitates bone marrow evaluation 1, 3

Additional Testing Based on Clinical Context

• Basic coagulation studies (PT, aPTT, fibrinogen, D-dimers) should be obtained to evaluate for DIC in patients with severe thrombocytopenia 3, 5
• Immunoglobulin measurement may identify common variable immune deficiency, as ITP can be its presenting feature 3, 2
• Iron studies (ferritin, transferrin saturation) distinguish iron deficiency-associated thrombocytopenia from other causes 6

Critical Pitfalls to Avoid

• Excluding pseudothrombocytopenia by repeating platelet count in heparin or sodium citrate tubes is essential, as EDTA-dependent platelet agglutination falsely lowers counts 1, 3, 2
• Platelet transfusions are contraindicated in TTP or type II heparin-induced thrombocytopenia, as they fuel thrombosis and worsen clinical outcomes 5
• Missing secondary causes of immune thrombocytopenia (HIV, HCV, SLE, lymphoproliferative disorders) leads to inappropriate treatment and poor outcomes 1, 3
• Overlooking medication-induced cytopenias requires comprehensive medication review including prescription, non-prescription drugs, and herbal supplements 1
• Delaying bone marrow examination in patients over 60 years or with atypical features risks missing life-threatening malignancies 1, 3