In a 30‑year‑old woman with abnormal uterine bleeding from a uterine fibroid, HIV infection on tenofovir, lamivudine, and dolutegravir, hemoglobin 9.8 g/dL and platelet count 20 × 10⁹/L, what is the next step in management and what are the differential diagnoses?

Immediate Management: Severe Thrombocytopenia Takes Priority

The next step is to immediately investigate the cause of severe thrombocytopenia (platelet count 20,000/µL) before addressing the fibroid-related bleeding, because this degree of thrombocytopenia poses a life-threatening hemorrhage risk and may represent HIV-related immune thrombocytopenia (ITP), drug-induced thrombocytopenia from antiretrovirals, bone marrow suppression, or thrombotic microangiopathy. 1

Differential Diagnosis for Thrombocytopenia in HIV-Positive Patients

HIV-Related Causes

• HIV-associated immune thrombocytopenia (ITP) is the most common hematologic manifestation of HIV infection, occurring in 10–30% of patients and resulting from antiplatelet antibodies and impaired platelet production. 1
• Bone marrow suppression from HIV itself can cause pancytopenia, though isolated thrombocytopenia is more typical of ITP. 1
• Thrombotic thrombocytopenic purpura (TTP) occurs more frequently in HIV-positive patients and presents with thrombocytopenia, microangiopathic hemolytic anemia, fever, renal dysfunction, and neurologic changes—check for schistocytes on peripheral smear and elevated LDH. 1

Medication-Related Causes

• Drug-induced thrombocytopenia from antiretrovirals is possible, though tenofovir, lamivudine, and dolutegravir are not commonly associated with severe thrombocytopenia; however, any medication can cause immune-mediated platelet destruction. 1

Fibroid-Related Anemia

• Iron deficiency anemia from chronic blood loss due to the uterine fibroid explains the hemoglobin of 9.8 g/dL but does not explain the thrombocytopenia—these are two separate processes requiring distinct evaluations. 2, 3

Immediate Diagnostic Work-Up

Laboratory Evaluation

• Complete blood count with differential and peripheral blood smear to assess for schistocytes (suggesting TTP), platelet clumping (pseudothrombocytopenia), and white blood cell morphology. 1
• Reticulocyte count to determine if anemia is due to chronic blood loss (elevated reticulocytes) versus bone marrow suppression (low reticulocytes). 1
• Serum iron studies (ferritin, serum iron, total iron-binding capacity, transferrin saturation) to confirm iron deficiency anemia from fibroid bleeding. 3, 4
• LDH, indirect bilirubin, haptoglobin, and direct Coombs test to evaluate for hemolysis if TTP is suspected. 1
• HIV viral load and CD4 count to assess disease control on current antiretroviral therapy, as uncontrolled HIV increases the risk of ITP. 1
• Coagulation studies (PT, aPTT, fibrinogen) to exclude disseminated intravascular coagulation or other coagulopathies. 5

Imaging and Gynecologic Evaluation

• Transvaginal ultrasound combined with transabdominal imaging to confirm fibroid size, location, and endometrial thickness, and to exclude other structural causes of bleeding. 2, 6
• Endometrial biopsy is deferred until platelet count is corrected above 50,000/µL to minimize bleeding risk during the procedure. 2

Management Algorithm

Step 1: Stabilize Platelet Count

• If platelet count is <20,000/µL and patient has active bleeding or requires invasive procedures, administer platelet transfusion to raise count above 50,000/µL. 1
• Initiate corticosteroids (prednisone 1 mg/kg/day) if HIV-associated ITP is suspected, as this is first-line therapy and typically produces a response within 7–10 days. 1
• Ensure antiretroviral therapy is optimized (confirm adherence to tenofovir, lamivudine, and dolutegravir), as viral suppression improves platelet counts in HIV-related ITP. 1
• Consult hematology urgently for consideration of intravenous immunoglobulin (IVIG) if platelet count remains critically low despite corticosteroids, or if TTP is confirmed (requiring plasma exchange). 1

Step 2: Correct Anemia

• Start oral iron supplementation (ferrous sulfate 325 mg three times daily) immediately to address iron deficiency anemia from chronic fibroid bleeding. 7, 3, 4
• Consider intravenous iron (e.g., iron sucrose or ferric carboxymaltose) if oral iron is not tolerated or if rapid correction is needed before surgery. 7, 4
• Transfuse packed red blood cells only if hemoglobin drops below 7 g/dL or if patient is symptomatic (severe fatigue, dyspnea, tachycardia). 8

Step 3: Control Fibroid-Related Bleeding

• Initiate tranexamic acid (1,300 mg orally three times daily during menstruation) as a nonhormonal agent to reduce menstrual blood loss by 40–50% without affecting platelet count. 7, 6, 3
• Add NSAIDs (e.g., ibuprofen 400 mg three times daily for 5–7 days during bleeding episodes) for modest reduction in menstrual blood loss and pain control. 7, 6
• Defer hormonal therapy (levonorgestrel IUD, combined oral contraceptives, or GnRH antagonists) until thrombocytopenia is investigated and corrected, as some hormonal agents may theoretically increase thrombotic risk in the setting of severe thrombocytopenia. 7, 6

Step 4: Definitive Fibroid Management (After Platelet Recovery)

• Once platelet count is stable above 50,000/µL, proceed with endometrial biopsy to exclude hyperplasia or malignancy, as abnormal uterine bleeding in a 30-year-old with risk factors warrants tissue diagnosis. 2
• Initiate GnRH antagonist therapy (relugolix, elagolix, or linzagolix) with estrogen/progestin add-back as the most effective medical option for reducing fibroid volume and controlling bleeding after first-line therapies. 7, 6
• Consider surgical options (myomectomy or hysterectomy) if medical management fails after 3–6 months or if patient desires definitive treatment. 6, 4

Critical Pitfalls to Avoid

• Do not attribute thrombocytopenia to fibroid bleeding—fibroids cause anemia but not low platelets; failure to investigate thrombocytopenia separately may miss life-threatening conditions like TTP or severe ITP. 1, 5
• Do not perform endometrial biopsy with platelet count <50,000/µL—this poses unacceptable bleeding risk and must be deferred until platelet count is corrected. 2
• Do not start hormonal contraception without first ruling out structural causes of bleeding—transvaginal ultrasound is mandatory before initiating hormonal therapy to exclude malignancy or other pathology. 2, 6
• Do not delay hematology consultation—severe thrombocytopenia in an HIV-positive patient requires urgent specialist input to differentiate ITP from TTP or drug-induced causes. 1