A 25-year-old African American woman comes to the office after experiencing increasingly heavy menstrual cycles for 3 months. The patient has also noticed that her gums frequently bleed when she brushes her teeth. Review of systems is positive for ongoing pain and stiffness in her hands and wrists that is partially responsive to ibuprofen. She is not taking any medications and has no known medical conditions. The patient is afebrile, blood pressure is 149/79 mm Hg, and pulse is 87/min. A nonpainful oral ulcer is present. Multiple petechiae are present on the upper arms and shins. The wrists and hands are tender to palpation and demonstrate reduced range of motion. Laboratory results are as follows:
| Hemoglobin | 10.8 g/dL |
| Platelets | 40,000/mm3 |
| Leukocytes | 2,500/mm3 |
| Serum creatinine | 1.7 mg/dL |
Which of the following is the most likely cause of thrombocytopenia in this patient?
Hematologic manifestations of SLE | ||
Common mechanisms | Uncommon mechanisms | |
Anemia |
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Leukopenia |
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Thrombocytopenia |
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MAHA = microangiopathic autoimmune hemolytic anemia; SLE = systemic lupus erythematosus; TTP = thrombotic thrombocytopenic purpura. | ||
This patient's presentation (joint pains, oral ulcer, hypertension, pancytopenia, impaired renal function) suggests possible systemic lupus erythematosus (SLE), a systemic autoimmune disorder. Her severe thrombocytopenia (platelet count <50,000/mm3), manifesting with common associated features of bleeding gums and heavy menstrual periods, is likely due to SLE. In the United States, SLE occurs most commonly in African American, Hispanic, and Asian women. Hematologic abnormalities occur in over half of SLE patients and include:
The presence of autoantibodies is the primary mechanism underlying the most common cytopenias in SLE. Thrombocytopenia is most often caused by antiplatelet antibodies, which trigger increased destruction of platelets via immunoglobulin binding in peripheral blood vessels and subsequent macrophage phagocytosis. Less commonly, thrombocytopenia can occur in SLE-associated hypercoagulable states in which platelets are consumed within thrombi (eg, thrombotic thrombocytopenic purpura, associated with schistocytes; disseminated intravascular coagulation, which can occur in antiphospholipid antibody syndrome).
(Choice A) Although splenic sequestration of immunoglobulin-bound platelets may occur downstream, the primary initiating mechanism for platelet destruction in SLE occurs in peripheral blood vessels via the abnormal formation of immune complexes. In contrast, aberrant splenic sequestration occurs in conditions that increase portal pressure and splenic congestion, such as liver disease, hepatic vein thrombosis, or sickle cell anemia. Typically, the thrombocytopenia associated with these conditions is mild (60,000-150,000/mm3).
(Choices B and D) Malignant invasion of bone marrow, seen in leukemias and lymphomas, may cause pancytopenia. Similarly, pancytopenia can be caused by ineffective hematopoiesis resulting from primary bone marrow disorders (eg, myelodysplastic syndrome, aplastic anemia). However, these conditions are unlikely to explain this patient's new kidney disease, hypertension, nonpainful oral ulcer, and arthralgias.
(Choice C) Dilutional thrombocytopenia can occur following massive transfusion of packed red blood cells or large-volume intravenous fluid resuscitation, in which plasma volume is increased disproportionately to platelet count. This patient has no history of either procedure.
Educational objective:
Pancytopenia (decreased red blood cells, white blood cells, and platelets) is common in patients with systemic lupus erythematosus. It usually indicates concurrent peripheral, immune-mediated destruction of all 3 cell lines.