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  IN THIS Article
 ::  Abstract
 ::  Introduction
 ::  Case report
 ::  Discussion
 ::  References

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CASE REPORT
Year : 1996  |  Volume : 42  |  Issue : 3  |  Page : 88-90

Hemostasis in acquired hemophilia--role of intracavitary instillation of EACA.


Department of Dr J C Patel Hematology, KEM Hospital, Parel, Mumbai.

Correspondence Address:
S S Sahu
Department of Dr J C Patel Hematology, KEM Hospital, Parel, Mumbai.

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Source of Support: None, Conflict of Interest: None


PMID: 0009715327

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 :: Abstract 

An 82 year old man developed antibodies against coagulation factor VIII:C without any apparent cause. Bleeding from the soft tissue cavity could not be controlled by factor VIII:C concentrates, immunosuppression with steroids and intravenous immunoglobulin therapy in the standard dosages. However, a single injection of Epsilon Aminocaproic Acid (EACA) instilled into the cavity under aseptic precautions achieved lasting hemostasis with resultant wound healing.


Keywords: 6-Aminocaproic Acid, therapeutic use,Aged, Aged, 80 and over, Antifibrinolytic Agents, therapeutic use,Autoantibodies, immunology,Case Report, Factor VIII, immunology,Hemophilia A, complications,immunology,Hemorrhage, drug therapy,etiology,Human, Instillation, Drug, Male,


How to cite this article:
Sahu S S, Raipancholia R R, Pardiwalla F K, Pathare A V. Hemostasis in acquired hemophilia--role of intracavitary instillation of EACA. J Postgrad Med 1996;42:88-90

How to cite this URL:
Sahu S S, Raipancholia R R, Pardiwalla F K, Pathare A V. Hemostasis in acquired hemophilia--role of intracavitary instillation of EACA. J Postgrad Med [serial online] 1996 [cited 2019 Aug 21];42:88-90. Available from: http://www.jpgmonline.com/text.asp?1996/42/3/88/428





  ::   Introduction Top


Spontaneous development of autoantibodies against factor VIII: C in a nonhemophiliac is a rare but significant clinical occurrence that frequently is associated with life threatening complications[1],[2].

Therapeutic options for this condition continue to expand' and the choice of an optimal regimen for each patient is based on many considerations. These include the level of the inhibitor, underlying disease state clinical responses to previous treatment, degree of antibody interaction with the patients factor VIII: C, and most important the cost and availability of an effective therapeutic modality.

This article describes the role of EACA instillation as a hemostatic agent in controlling bleeding manifestations due to factor VIII: C antibodies in a patient of acquired hemophilia.


  ::   Case report Top


AP, a 82 year old man was admitted under orthopaedic care with a history of moderate fever, chills and rigors. He had a painful, tender swelling in the left gluteal region, which was clinically diagnosed as cellulitis evolving into an abscess. He received appropriate antibiotics; but as the swelling did not subside, it was incised. This revealed an intramuscular hematoma, drainage of which resulted in a large soft tissue cavity extending from the gluteal region upto the lower third of the posterior thigh. Post-evacuation, as the patient bled persistently, hematological assistance was sought. It thus came to light that the patient had auto-antibodies against factor VIII: C which were the cause of his bleeding diathesis. On inquiry, his past and family history was non-contributory. Incidentally, a year ago he had undergone a major dental procedure to remove all his teeth without any form of supportive treatment or excessive bleeding. The rest of his systemic examination was unremarkable.

His investigation revealed Hb 9.5g/dl, WBC Count 12 X 109/L, platelet count 400 X 109/L, Bleeding time 4'. (Ivy), Prothrombin time (c/p) 15/15, activated partial thromboplastin time (c/p) 41"/115" which did not correct with an equal quantity of normal pooled plasma. Factor VIII: C was < 1.0% of control and F VIII inhibitor titer was 1.8 BU. Liver function tests, renal chemistry, serum electrolytes, acid and alkaline phosphatase, Blood sugar and triglycerides were normal. Collagen vascular work-up, RA; LE cell preparation, HbsAg and HIV were negative. Serum immunoglobulins revealed a polyclonal elevation of all traction with a normal electrophoretic pattern. There was no evidence of an underlying malignancy.

The patient was given F VIII: C concentrates; 7,500 units (90% correction) as a bolus, in the hope of overriding the low titer inhibitor but he behaved like a high responder with a resultant rise of his inhibitor titer to 512 BU with persistent bleeding manifestations. Factor VIII: C concentrates were hence discontinued and immunosuppressive therapy with prednisolone (1 mg/kg) was initiated. However, he soon developed wound sepsis, which was controlled by appropriate antibiotics, although steroids had to be discontinued. His bleeding manifestations however persisted. It was therefore decided to administer intravenous immunoglobulins in the dose of 400 mg/ kg for five successive days (along with factor VIII: C at 90% correction; 7,500 units) but he still continued to bleed requiring packed red cell transfusions. A single instillation of 20 cc 25% EACA into the wound however achieved lasting hemostasis and was followed by complete healing.


  ::   Discussion Top


Autoantibodies directed against factor VIII: C are often associated with serious and fatal bleeding[1],[2]. Prediction of inhibitor potency, degree of clinical severity and the optimal choice of therapy are issues yet to be resolved satisfactorily. Chemotherapy with steroids or cyclophosphamide in combination with factor VIII: C concentrate is one management strategy that has produced frequently encouraging results in suppressing the inhibitor actively with good clinical outcome[4]. However, cytotoxic therapy to suppress inhibitor formation is most effective in dealing with low titer inhibitors[5]. Nonetheless, this strategy did not help our patient who behaved quite differently.

An innovative and promising approach to the treatment of factor VIII: C antibodies involve the infusion of human polyspecific immunoglobulins[6]. It has been hypothesised that the immunoglobulin preparation contains anti-idiotype antibodies which recognise the key F (ab) domains on the factor VIII: C inhibitor protein and so complex with them so as to neutralise their inhibitory capacity[6]. However, although intravenous immunoglobulins are useful in most patients with spontaneous factor VIII: C inhibitors some complete failures have also been observed[6],[7], Unfortunately, our patient who did not show the desired response, falls into the latter category.

In 1980, porcine factor VIII: C became available for clinical usage and was immediately hailed as a safe and effective means to attain hemostasis[6],[7],[9]. Moreover, it is devoid of impurities like vWF and platelet activating factor and could be used repeatedly in view of the minimal cross-reactivity. The only drawback was its exorbitant cost and free availability. Incidentally, although our patient could have certainly afforded, the cost it was not available locally.

Inactivated and activated factor IX complex concentrates have been used to control bleeding complications in acquired hemophilia with variable success[1]. Unfortunately, these products have not been effective in all inhibitor patients and may be variably effective in the same patient requiring changes in product choice to achieve adequate hemostasis. Moreover, transmission of hepatitis and human immunodeficiency virus has been of additional concern. Furthermore, by virtue of their contamination by activated clotting factors, this treatment may precipitate episodes of hypercoagulability including lethal pulmonary embolism, myocardial infarction, cerebrovascular accidents, and disseminated intravascular coagulation in otherwise normal healthy patients. This was the main objection in withholding this therapeutic option in our elderly patient. Antifibrinolytic agents have been used to achieve hemostasis in a variety of clinical settings[1],[10],[13]. In hemophiliacs, they are of value both in the prophylaxis and treatment of bleeding from mucus membranes, particularly in connection with dental extractions, nose and gum bleeds, and menorrhagia[3]. In this setting, it is a safe, cheap and easily available modality of therapy. Our patient showed a dramatic response to a single injection of EACA instilled with utmost sterile precautions in the soft tissue cavity through the open wound resulting in the total obliteration of the potential cavity spase, permanent and lasting hemostasis followed by complete would healing. At present, the patient still has a low titer inhibitor (2 BU) but is absolutely asymptomatic.

 
 :: References Top

1. Kessler CM. An introduction to factor VIII inhibitors. The detection and quantification. Am J Med 1991; 91 (Suppl 5A) 1:1-5  Back to cited text no. 1    
2.Lottenburg R, Kentro TB, Kitchins CS. Acquired hemophilia, A natural history study of 16 patients with factor VIII inhibitor receiving little or no therapy. Arch Intern Med 1987; 147:1077-1081.  Back to cited text no. 2    
3.Hoyer LW. Future approaches to factor VIII inhibitor therapy, Am J Med 91 (Suppl 5A) 1991; 40-44.  Back to cited text no. 3    
4.Lusher JM. Perspectives on the use of factor IX complex concentrates in the treatment of bleeding in persons with acquired factor VIII inhibition. Am J Med 1991; 91(Suppl 5A)30-4  Back to cited text no. 4    
5.Green D. Cytotoxic suppression of acquired factor VIII: C inhibitors. Am J Med 91 (Suppl 5A)1991; 14-19.  Back to cited text no. 5    
6.Kernoff PBA, Thomas ND, Lilley PA, Mattews KB, Goldman E, Tuddenham EGD. Clinical experience with polyelectrolyte-fractionated porcine factor VIII concentrate in the treatment of hemophiliac with antibodies to factor VIII Blood 1984; 63:31-34.  Back to cited text no. 6    
7.Sultan Y, Kazatchkine Z, Lydegger U, Rossi F, Dietrich, Algiman M. Intravenous immunoglobulin in the treatment of spontaneous acquired factor VIII:C inhibitors. Am J Med 1991; 91(Suppl 5A):35-39.  Back to cited text no. 7    
8.Brettler DB, Forsberg A, Levine PH, Aledort LM, Hilgartner MW, Kasper CK, Lusher JM, McMillan C, Roberts H, et al. The use of Porcine factor VIII concentrate (Hyate C) in the treatment of patients with inhibitor antibodies to factor VIII: C. A multicenter U.S. trial Arch Intern Med 1989; 149:1381-1383.  Back to cited text no. 8    
9.Hay CRM. Innovative use of porcine factor VIII: C for immune tolerance induction. Am J Med 1991; 91 (Suppl 5A):27-29.  Back to cited text no. 9    
10.Coggins JT, Alien TD. Insoluble clots within the urinary tract as a consequence of epsilon aminocaproic acid therapy J Urol 1972; 107:647-650.  Back to cited text no. 10    
11.Collen D. On the regulation and control of fibrinolysis. Thromb. Haemost 1980; 43:77-79.  Back to cited text no. 11    
12.Forbes CD, Barr RD, Reid G, Thomson C, Prentice CRM, McNicol GP, Douglas AS, et al. Transexamic acid in control of haemorrhage after dental extracton in haemophilia and Christmas disease. Br Med J 1972; 2:311-313.  Back to cited text no. 12    
13.Prentice CRM. Indications for antifibrinolytic therapy. Thromb Diath Haemorr 1975; 14:630-632.   Back to cited text no. 13    



This article has been cited by
1 Role of epsilon amino caproic acid in the management of haemophilic patients with inhibitors
Ghosh K, Shetty S, Jijina F, et al.
HAEMOPHILIA. 2004; 10 (1): 58-62
[Pubmed]



 

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Online since 12th February '04
2004 - Journal of Postgraduate Medicine
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