April 2021 — Transfusion Medicine
A middle-aged woman with a history of an autoimmune disorder and endocarditis presents to the ED with severe abdominal pain and neurologic defects. Imaging reveals multiple infarcts involving the abdominal viscera. An echocardiogram is negative. Lab values: creatinine 2.11mg/dL, Hgb 9.0 g/dL, PLT 64,000, PT 61.3, aPTT 32, dsDNA Ab 182 (H), beta-2 glycoprotein 1 IgG 69.9 (H), phospholipid Ab IgG 56.0 (H), DRVVT confirm >1.2, and ADAMTS13 activity >90%. Renal biopsy is pending. There is no history of recent hospitalization or medications.
Given the above information, what is the most likely diagnosis?
- Cardioembolic event secondary to endocarditis
- Antiphospholipid syndrome (APS)
- Thrombotic thrombocytopenic purpura (TTP)
- Catastrophic antiphospholipid syndrome (CAPS)
The correct answer is ...
The correct answer is: catastrophic antiphospholipid syndrome (CAPS).
Catastrophic antiphospholipid syndrome (CAPS) is an autoimmune process characterized by diffuse vascular occlusion secondary to anti-phospholipid antibodies. According to Asheron et al., the diagnostic criteria for CAPS includes:
- Evidence of involvement in >/= 3 organs
- Development of symptoms simultaneously or in <1 week
- Laboratory evidence of persistent antiphospholipid antibodies (lupus anticoagulant and/or anticardiolipin antibodies), at least 6 weeks apart
- Histopathologic confirmation of small vessel occlusion in at least one organ, with or without associated vasculitis
Clinical manifestations of CAPS are the result of multi-organ ischemia/infarction. Patients may present with respiratory failure (acute respiratory distress syndrome or diffuse alveolar hemorrhage), stroke, acute renal failure, adrenal insufficiency, and cutaneous infarction. Based on the CAPS Registry, most patients with CAPS are women in their late thirties with manifestations usually triggered by a precipitating event (infection, surgery, drugs, etc.). The patient in the question stem is of the usual age/gender and demonstrated clinical evidence of involvement in >/= 3 organs (multi-organ infarction) within 24 hours. In conjunction with elevated antiphospholipid antibodies and the pending renal biopsy, a diagnosis of CAPS is most likely.
A triple-therapy strategy has reduced CAPS-associated mortality from 50% to 30%. This strategy includes heparin, high-dose glucocorticoids, and either IVIG or therapeutic plasma exchange (TPE). TPE is performed daily for a minimum of 3-5 days with plasma as replacement fluid. Plasma is thought to be beneficial as it provides natural anticoagulants including protein C, protein S, and antithrombin, the latter required for heparin-mediated anticoagulation.
The Sydney Investigational Criteria lists diagnostic criteria for antiphospholipid syndrome (APS). These criteria include both clinical and laboratory findings. Clinical findings include otherwise unexplained obstetrical complications (recurrent miscarriage, stillbirth, preeclampsia, intrauterine growth restriction, etc.) and definitive evidence of vascular thrombosis (either by imaging or histopathology). Laboratory findings include medium/high titer anti-cardiolipin or anti-beta-glycoprotein IgG/IgM and demonstration of persistent lupus anticoagulant. Subtle but important differences in the diagnosis of APS (as compared to CAPS) include demonstrating persistent lupus anticoagulant over at least a 12-week period and the absence of vasculitis on microscopy. APS is generally treated with long-term anticoagulation, including warfarin, heparin (during gestation), and direct-acting oral anticoagulants (for venous thrombosis only).
Given the negative transesophageal echocardiogram, a cardioembolic event is less likely. ADAMTS13 activity is within normal limits, thereby excluding a diagnosis of thrombotic thrombocytopenic purpura. A diagnosis of heparin-induced thrombocytopenia (HIT) may be considered. However, as the patient was not previously hospitalized and was not taking any medications, a diagnosis of HIT is unlikely.
- Asherson RA, Cervera R, de Groot PG, Erkan D, Boffa MC, Piette JC, Khamashta MA, Shoenfeld Y; Catastrophic Antiphospholipid Syndrome Registry Project Group. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus, 2003;12(7):530-4. doi: 10.1191/0961203303lu394oa. PMID: 12892393.
- “Clinical Manifestations of Antiphospholipid Syndrome.” UpToDate, www.uptodate.com/contents/clinical-manifestaions-of-antiphospholipid syndrome?source=history_widget
- Padmanabhan, Anand, et al. “Guideline on the Use of Therapeutic Apheresis in Clinical Practice – Evidence – Based Approach from the Writing Committee of the American Society for Apheresis: The Eighth Special Issue.” Journal of Clinical Apheresis, vol. 34, no. 3, 2019, pp. 171-354., doi: 10.1002/jca.21705
- Shaz, Bet, et al. Transfusion Medicine and Hematostasis: Clinical and Laboratory Aspects. Elsevier Science, 2019.
Michael McCarthy, M.D.
Resident, Anatomic and Clinical Pathology
Margaret DiGuardo, M.D.
Senior Associate Consultant, Transfusion Medicine