A 49-year-old male with thrombocytopenia, abdominal pain and gross hematuria.

CASE PRESENTATION

A 49-year-old Caucasian man presented with right upper quadrant (RUQ) pain, initially thought to be related to cholecystitis.  Past medical history was significant for ITP for 10 years treated with steroids in the past and more recently with IVIg and Rho(D) Immune Globulin (when platelet counts declined to <50K), deep venous thrombosis (12 years prior), lower abdominal aortic thrombosis requiring stent placement 3 years prior, and hypertension of <1 year duration. The patient did not report taking any medications on a chronic basis. Physical exam revealed a BP of 158/78, pulse 80 bpm, temperature 99.7 F, malar rash, and RUQ tenderness. On the day of admission, for the first time, the patient noted gross hematuria. Laboratory evaluation disclosed a creatinine of 1.4 mg/dl (baseline sCr 1.2 mg/dl 6 months prior), hematocrit 33%, WBC 9K, and platelet count 56K. Urinalysis revealed 1+ protein, many RBC’s/hpf, 5-10 WBC’s/hpf, and no cellular casts. Positive serologies included a low-titer ANA, high-titer anti-RNP antibody, lupus anticoagulant, and high-titer IgM and IgG anti-cardiolipin antibody. Negative serologies included anti-DNA antibody, anti-Smith antibody, ANCA, HBsAg, HCVAb, and HIV. The patient had markedly depressed C3 and C4 complement levels. One day following admission the creatinine increased to 1.7 mg/dl and renal biopsy was performed.

RENAL BIOPSY FINDINGS

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PATHOLOGY DIAGNOSIS

Thrombotic microangiopathy involving glomeruli and arterioles, acute & severe, associated with extensive renal cortical infarction (Catastrophic Anti-Phospholipid Syndrome-Associated/Clinical).

CLINICAL FOLLOW UP

Two days post-biopsy, the patient’s creatinine increased to 6.0 mg/dl. Abdominal CT scan revealed bilateral renal infarcts and splenic infarction.  A CT scan of the head revealed numerous small infarcts in multiple vascular territories. Two months post-biopsy, the patient remains dialysis-dependent, but is able to perform almost all activities of daily living.

DISCUSSION

Thrombotic microangiopathy (TMA) can be caused by a variety of seemingly unrelated conditions that are linked by their ability to damage endothelium, leading to microthrombosis.  Causes of TMA include TTP/HUS, pre-eclampsia, post-partum renal failure, antiphospholipid syndrome, malignant hypertension, scleroderma, and drug-induced and hereditary forms of disease. Pathologic findings in acute TMA include glomerular, arterial, and arteriolar fibrin thrombosis, endothelial swelling (“endotheliosis”), red blood cell congestion, mucointimal edema of arteries & arterioles, and, in severe cases, cortical necrosis. Subacute and chronic changes associated with TMA include GBM duplication with cellular interposition, mesangiolysis, organization of thrombi, and concentric onionskin-type fibroplasia of blood vessels.??Antiphospholipid antibody syndrome (APLS) is caused by antibodies against phospholipids or plasma proteins bound to anionic phospholipids, subsequently leading to thrombosis.  APLS may be primary/idiopathic or may occur secondary to SLE, other rheumatic diseases, infection, or medications. The diagnosis of APLS requires the presence of one clinical and one laboratory criterion. Clinical criteria for APLS include evidence of arterial or venous thrombosis, and obstetric complications such as multiple unexplained first trimester miscarriages or premature births. Laboratory criteria require documentation of antiphospholipid antibodies on two separate occasions, at least 12 weeks apart.  The antiphospholipid antibody tests most commonly performed include screening for lupus anticoagulant (LAC) and/or ELISA tests for IgG and/or IgM anticardiolipin antibodies or beta-2-glycoprotein antibodies.  The mainstay of treatment for APLS is anticoagulation.??Rarely, patients with APLS develop severe, life-threatening disease which has been referred to as catastrophic APLS. Criteria for the diagnosis of catastrophic APLS include involvement of 3 or more organs, development of manifestations over a time period of no more than one week, histologic confirmation of thrombosis, and laboratory confirmation of the presence of antiphospholipid antibodies. Optimal therapy for catastrophic APLS has not been defined. In addition to anticoagulation, steroids and other immunosuppressive agents, plasmapheresis, and IVIg have been used with some success.  Precipitating events, such as infection, lupus flare, or malignancy, should be sought and aggressively treated. Even with aggressive therapy, mortality for catastrophic APLS approaches 50%.

REFERENCES

Miyakis, S, Lockshin, MD, Atsumi, T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4:295.

Asherton RA, Cervera R, de Groot PG et.al. Catastrophic antiphospholipid syndrome: international consensus statement on classification criteria and treatment guidelines. Lupus 2003; 12(7): 530-534.

Cervera R, Asherton RA. Catastrophic antiphospholipid syndrome. J Pathophys Haemost Thromb 2006; 35 (1-2):181-6.

CORRESPONDANCE

Leal Herlitz MD (1), Xiaolei Zhu MD, PhD (2), Jeffrey L. Vacirca MD (3), Glen Markowitz MD(4)
(1) Department of Pathology, Columbia University, (2) Kidney Doctors PLLC, Port Jefferson, New York. (3) North Shore Hematology/Oncology Associates PC, New York