Pain, Anxiety, and Dementia: A Catastrophic Outcome

Generalized somatic pain persisted the morning after the surgical biopsy, but the patient remained clinically unchanged. An hour later, he was found unresponsive with no pulse. Despite extensive resuscitative efforts, the patient died.

Postmortem

There was a high index of suspicion for a hemostatic perturbation given the skin findings and recent manipulation of anticoagulation with a prior thrombotic event. The axillary lesion closely resembled warfarin-related skin necrosis. Management included enoxaparin with supportive care, pending definitive pathologic findings.

Postmortem examination confirmed diffuse multiorgan involvement similar to the process seen in the thigh biopsy. Ischemic injury secondary to small vessel microthrombi were evident in the skin, subcutaneous fat, large bowel, urinary bladder, and associated pericystic fat (Figure 1B). Interpretation of the surgical thigh biopsy became available after the patient died. It demonstrated infarcted fat with fat necrosis and hemorrhage (Figure 2).

The results of the laboratory investigations for thrombophilia also came back after the patient died. A potent lupus anticoagulant (LA) was demonstrated. It manifested primarily in the intrinsic pathway as a strongly positive LA-sensitive-aPTT (delta time = 20.5 seconds) assay with a weakly positive dilute Russell’s viper venom time assay. The antigenic specificity of the LA antibodies was not uncovered, as the plasma levels of both IgM and IgG anticardiolipin and anti-Β2-glycoprotein-I antibodies were within the reference range. Factor (F) II and FV genotyping revealed wild-type FV, and the prothrombin gene G20210A was without mutation.

Assays for plasma levels of protein S and antithrombin activity were also normal, which excluded deficiencies in these proteins. The assay for protein C activity was slightly decreased. This may have exacerbated the hemostatic imbalance caused by the LA, as the FVII level had normalized. However, the etiology of the protein C deficiency is not clear. Considerations include (1) a warfarin disequilibrium state due to the discontinuation of oral anticoagulation and institution of vitamin K therapy; (2) an epiphenomenon resulting from active thromboses; or (3) a possible hereditary protein C deficiency.

The definitive diagnosis of the catastrophic antiphospholipid antibody (APA) syndrome relies on multiorgan failure in < 1 week, histopathologic evidence of small vessel thrombosis, and a positive LA.¹ The study patient fulfilled these criteria (Table).

DISCUSSION

Catastrophic progression of APA syndrome is an infrequent and devastating complication of this autoimmune disorder with a mortality rate of nearly 50%.¹ Antiphospholipid antibody syndrome typically presents with thromboses of the larger vessels, and it more commonly affects the venous system. In contrast, diffuse small vessel thromboses underlie the pathogenesis of catastrophic APA syndrome (CAPS).² This catastrophic progression occurs in < 1 out of 100 patients with the APA syndrome, more frequently in women (69%), and over an age range of 7 decades (mean 38 years).² A case series analysis identified older age (aged > 36 years), history of systemic lupus erythematous, and broader organ involvement as prognostic indicators of a poor outcome. Better outcomes are associated with thrombocytopenia and anticoagulation treatment. However, gender did not influence mortality.³

Prevention is key to APA management, given the lack of efficacious treatment.² Preventive measures are focused on avoiding triggers and aggressively treating those triggers that may arise. Possible triggers in this case included cessation of anticoagulation due to hematochezia and in anticipation of surgery, infection (C difficile colitis, suspected necrotic skin wound super infection, and a UTI), and biopsy-related trauma.

Initial clinical stability in this patient with abrupt decompensation along with pending laboratory and pathology results limited the opportunity for more aggressive therapeutic intervention for CAPS. Moreover, the relative sparing of the cardiopulmonary and renal systems contrasted with the more classical systemic involvement usually seen in CAPS. Second-line therapies for CAPS include plasma exchange and high-dose steroids.² Third-line therapeutics include immunosuppressive agents, such as cyclophosphamide.²

The rapid decompensation, described on postoperative day 1, after a low-risk surgical biopsy highlights the importance of perioperative care in patients with this autoimmune condition. Following a review of surgical cases, Erkan and colleagues concluded that standard antithrombotic regimens for general and orthopedic surgery are likely to undertreat patients with APA syndrome.⁴ They recommend the following guidelines in place of standard antithrombotic management: preoperative platelet count > 100 k/µL, higher threshold before proceeding with surgery/interventional procedures, limiting intravascular manipulations, and minimizing periods without anticoagulation therapy.⁴

A case report of a 31-year-old female undergoing mitral valve replacement complicated postoperatively by CAPS-associated biventricular failure, despite preoperative transition of warfarin to unfractionated heparin, illustrates this significant perioperative risk.⁵ Evidence-based guidelines recommend holding enoxaparin 24 hours before surgery and 24 hours after invasive procedures in patients requiring bridging anticoagulation therapy.⁶