Prophylactic and perioperative replacement therapy for acquired factor XIII deficiency

Abstract

To cite this article: Lim W, Moffat K, Hayward CPM. Prophylactic and perioperative replacement therapy for acquired factor XIII deficiency. J Thromb Haemost 2004; 2: 1017-19. Acquired factor (F)XIII deficiency is a rare coagulation disorder with limited information on using laboratory assays to guide management. We encountered unique monitoring and therapeutic challenges while managing a 73-year-old man with acquired FXIII deficiency. He presented with an extensive leg hematoma after receiving low-molecular-weight heparin for a suspected calf vein thrombosis. Two years earlier, he had developed a leg hematoma while on warfarin, which was discontinued. His medical history included inactive rheumatoid arthritis, stable angina, and paroxysmal atrial fibrillation on amiodarone. There was no family or prior bleeding history. He had previously undergone tonsillectomy, cholecystectomy and dental extractions without incident. Coagulation tests indicated an isolated deficiency of FXIII, with no FXIII activity detectable by the urea clot solubility assay [1,2] , twice weekly). A portacath was placed for home replacement therapy. Amiodarone was discontinued due to concerns about a drug-induced FXIII inhibitor.Six months later, the patient developed increasing angina. Angiography revealed a 90% stenosis of the left anterior descending coronary artery and a single coronary artery bypass graft was recommended. His FXIII inhibitor titer remained low (< 2 BU) and preoperative FXIII survival studies confirmed accelerated FXIII clearance, with more rapid decay of FXIII activity compared with FXIIIA antigen (Fig. 1A). Bypass surgery was done using off-pump, beating heart surgery to minimize risks of a postoperative coagulopathy. Perioperatively, FXIII levels were monitored using the Berichrom assay, as no other rapid commercial assays were available. He was given 2500 U FXIII (42 U kg ) immediately before and after surgery, and again on postoperative days 1-3, 5-7 and 9, before resuming his usual prophylaxis (2500 U twice weekly), which normalized his FXIII activity during surgery and maintained levels above 0.40 U mL )1 for 7 days postoperatively (Fig. 1B). No abnormal bleeding occurred and he recovered fully without complications. Over the subsequent 38 months, his FXIII inhibitor has remained < 2 BU and he has been maintained on lower doses of FXIII prophylaxis and aspirin 80 mg daily, without further angina or serious bleeding.He had a few minor bleeds when his FXIII prophylaxis was reduced to the point that no predose FXIII activity was detectable by urea clot solubility assays, but this resolved when his prophylaxis was adjusted to provide residual FXIII activity (1750 U, 29 U kg )1 weekly).FXIII is important for stabilizing fibrin and making clots less susceptible to plasmin lysis [5][6][7]. Inhibitors arising from replacement therapy in congenital FXIII deficiency are rare, and inhibitors causing acquired FXIII deficiency are 10 times as rare as congenital FXIII deficiency [8]. Acquired FXIII deficiency has been report...

Prophylactic and perioperative replacement therapy for acquired factor XIII deficiency: a rebuttal

“…Germany) consistently detected FXIII activity in the range of 8-14% [1]. The same observation was made with the plasma of three other individuals suffering from severe congenital FXIII deficiency.…”

“…The aberrant mRNA splicing observed in our hemophilia B patient supports a mechanism of polypyrimidine tract shortening and/or elimination of a specific binding site essential for spliceosome formation. Contrary to previous reports in this journal [1,2], the results presented here indicate that perhaps full-length FIX transcript is produced as illegitimately transcribed mRNA derived from peripheral blood leukocytes and is therefore a useful tool for the analysis of genetic defects involving splicing abnormalities. Prophylactic and perioperative replacement therapy for acquired factor XIII deficiency: a rebuttal…”

Successful Management of a Patient with Autoimmune Hemorrhaphilia due to Anti-Factor XIII/13 Antibodies Complicated by Pulmonary Thromboembolism

“…Incidentally, the abovementioned AH13 cases had variable FXIII inhibitor titers between <2 [18] and 30 BU/mL [13]. Accordingly, AH13 cases with FXIII inhibitor can develop thromboembolism regardless of the titer, either high or low.…”

“…Unfractioned heparin was administered to the present case. Cases 1 and 2 were managed with low-molecular-weight heparin [18,19], while case 3 received a filter in the IVC without anticoagulation therapy [13]. Thrombosis in AH13 patients requires careful mild anticoagulation therapy to prevent the possible exacerbation of bleeding tendencies.…”

“…The first case was a 73-year-old man with suspected calf vein thrombosis [18], the second case was a 77-year-old woman with thromboses in the left internal jugular vein and in the right popliteal vein [19], and the third case was a 65-year-old man with left femoral DVT and PE [13]. The venous thromboses in cases 1 and 2 seemed to have occurred spontaneously, while the DVT and PE in case 3 occurred after the patient received plasma-derived FXIII concentrates and antifibrinolytic drugs, i.e., tranexamic acid [13].…”