Case Reports S K I N NECROSIS WITH A LOU’ MOLECULAR WEIGHT H E P A K I N
The prophylactic low dose heparin for deep venous thrombosis (DVT) in the care schedule after major surgery procedures-introduced by Shanoff & DeHlasio ( 197O)-is a well-contrastated therapeutic approach. Nevertheless. several complications of using heparin as phrophylaxis for DVT and subsequent pulmonary embolism have been emerging. The most important and frequent complications are the haemorrhagic ones. Occasionally. thrombocytopenia andlor skin necrosis have been reported (White et nl. 1979: Bell & Koyal. 1980; Armengol rt a!. 1989).Kecently. several new approaches have been investigated to improve the efficacy of low dose heparin and reduce the frequency of complications. In this sense. new drugs derived from original high molecular weight heparin have been introduced for routine therapeutic use. The use of low molecular weight heparins (LMWH) as prophylaxis for DVT have been advocated on the basis of its lower secondary haemorrhagic effects and easier administration. At the moment. very few secondary effects have been reported with this kind of heparin. in spite of its increasing and widespread use. Recently. a heparin-induced skin reaction has been reported in a patient with previous heparininduced skin reaction who had a recurrence of the complication with LMWH (Manohararn, 1992). A skin necrosis with LMWH is now reported. The patient received a prophylactic schedule with Fraxiparina after a complete hip replacement. The patient, an obese 68-year-old female. was treated after a hip replacement procedure with the prophylactic schedule of LMWH (Fraxiparino) currently administered in our hospital to patients with high risk of developing IIVT. A daily dose of 0 . 3 nil of Fraxiparinz was administrated subcutaneously for 6 d. On the fifth day. a local erythema surrounding the puncture site appeared and some hours later it developed into a skin lesion and a necrotic ulcer was evident. In view of this c.omplication. the subcutaneous I.MI2‘H was interrupted and a continuous schedule of intravenous sodium heparin was started. Reforehand. a complete coagulation and prothrombotic state study was performed (including PT. APTT. TT. reptilase. tibrinogen (Klaus).FIIPs. l)-dimer. fibrin monomers (agglutination test). plasminogen. alfa-LAP, antithrombin III actiivity, protein S and C activity. euglobulin lysis time, tPA and f’,U-I antigen).and no pathological changes were seen. A few days later the patient ~ v a sdischarged on oral coumarin. A I)VT developed I 0 d after the skin necrosis episode, with the patient on oral couniarinic anticoagulation. It was confirmed by a phlebography study. The intravenous conventional heparin was restarted for a further 1 0 d. Daily platelet counts were performed and no thrombocytopenia was evident in serial blood samples. The skin necrosis is an unusual complication of the
subcutaneous administration of conventional heparin. Most of these cases are associated with thrombocytopenia and pulmonary thromboembolism. Some reports have described a protein S or C deficiency as a predisposing factor of skin ne(:rosis with oral anticoagulants (Craig et al, 1990). A similar predisposing factor has not been described in patients wi :h skin necrosis heparin-induced. After the availability of thr new LMWH. several authors theorized about the convenimce of switching to a LMWH schedule when thrombocytopenia and thrombosis appear (Godal, 1989). The correct procedure after a skin necrosis induced by heparin is not yet established. -n our case protein S and C levels were normal and no concomitant thrombocptopenia or thromboembolism ap 3eared: nevertheless. a DVT developed. Therefore, on the ba.;is of this one case, we are unable to recommend a switch from conventional heparin to LMWH after a cutaneous ne,:rosis.
KF.FEKF,NCES .\r.nengol. R.. More. [. X. ( h u . J. ( 1989) Heparin-induced skin ncc’rosis. thrornbocytopenia and pulmonary thrornboembolism. I’resentation of two cases. Mediririn Clinicn (Rurcriona), 9.3, (39% ‘-01 , Bell. \.\’.K. & Royal. R.M. ( 1980) Heparin-associated thrombocytopenia: a comparison of three heparin preparations. New England piirtrd of ,lltdi(.irw. 303, 902-904. (-raig. A..Taherner. DA., Fisher. A.H.. Foster. 1I.N. &Mitra,1. (1990) .rype I protein S deficiency and skin necrosis. Posfgruduutp Mcdicul ) o u t - t r d , 66. 389-391. G d a l . H.C. ( 1989) Heparin-induced thronibocytopenia. Heparin. ( ’ l i t 7 r t i i r a l mid Biological Properties. Clinical Applications (ed. by D. A. I,ane and II. Lindahll. chap. 2 5 . p. 542. Edward Arnold. Oxford. Slanoharan. A. ( 1992) Heparin-induced skin reaction with low inolecular-weight heparin. Europenrr joirrnnl of Huwinfohjy, 48. 2?4. Shdnott‘. J.G. & lle 131asio.G. ( 1 970) Prevention of fatal post-operative throinboenibolism by heparin prophylaxis. Lurrcet. ii, 1006. \!‘hire, K,\t’,, John. R.S. & Kichard. E.N. ( 1979) Thrombotic roruplication of heparin therapy including six cases of heparin induced skin necrosis. Arirmls oj’Snrgery, 190, 595-598.
The prophylactic low dose heparin for deep venous thrombosis (DVT) in the care schedule after major surgery procedures-introduced by Shanoff & DeHlasio ( 197O)-is a well-contrastated therapeutic approach. Nevertheless. several complications of using heparin as phrophylaxis for DVT and subsequent pulmonary embolism have been emerging. The most important and frequent complications are the haemorrhagic ones. Occasionally. thrombocytopenia andlor skin necrosis have been reported (White et nl. 1979: Bell & Koyal. 1980; Armengol rt a!. 1989).Kecently. several new approaches have been investigated to improve the efficacy of low dose heparin and reduce the frequency of complications. In this sense. new drugs derived from original high molecular weight heparin have been introduced for routine therapeutic use. The use of low molecular weight heparins (LMWH) as prophylaxis for DVT have been advocated on the basis of its lower secondary haemorrhagic effects and easier administration. At the moment. very few secondary effects have been reported with this kind of heparin. in spite of its increasing and widespread use. Recently. a heparin-induced skin reaction has been reported in a patient with previous heparininduced skin reaction who had a recurrence of the complication with LMWH (Manohararn, 1992). A skin necrosis with LMWH is now reported. The patient received a prophylactic schedule with Fraxiparina after a complete hip replacement. The patient, an obese 68-year-old female. was treated after a hip replacement procedure with the prophylactic schedule of LMWH (Fraxiparino) currently administered in our hospital to patients with high risk of developing IIVT. A daily dose of 0 . 3 nil of Fraxiparinz was administrated subcutaneously for 6 d. On the fifth day. a local erythema surrounding the puncture site appeared and some hours later it developed into a skin lesion and a necrotic ulcer was evident. In view of this c.omplication. the subcutaneous I.MI2‘H was interrupted and a continuous schedule of intravenous sodium heparin was started. Reforehand. a complete coagulation and prothrombotic state study was performed (including PT. APTT. TT. reptilase. tibrinogen (Klaus).FIIPs. l)-dimer. fibrin monomers (agglutination test). plasminogen. alfa-LAP, antithrombin III actiivity, protein S and C activity. euglobulin lysis time, tPA and f’,U-I antigen).and no pathological changes were seen. A few days later the patient ~ v a sdischarged on oral coumarin. A I)VT developed I 0 d after the skin necrosis episode, with the patient on oral couniarinic anticoagulation. It was confirmed by a phlebography study. The intravenous conventional heparin was restarted for a further 1 0 d. Daily platelet counts were performed and no thrombocytopenia was evident in serial blood samples. The skin necrosis is an unusual complication of the
subcutaneous administration of conventional heparin. Most of these cases are associated with thrombocytopenia and pulmonary thromboembolism. Some reports have described a protein S or C deficiency as a predisposing factor of skin ne(:rosis with oral anticoagulants (Craig et al, 1990). A similar predisposing factor has not been described in patients wi :h skin necrosis heparin-induced. After the availability of thr new LMWH. several authors theorized about the convenimce of switching to a LMWH schedule when thrombocytopenia and thrombosis appear (Godal, 1989). The correct procedure after a skin necrosis induced by heparin is not yet established. -n our case protein S and C levels were normal and no concomitant thrombocptopenia or thromboembolism ap 3eared: nevertheless. a DVT developed. Therefore, on the ba.;is of this one case, we are unable to recommend a switch from conventional heparin to LMWH after a cutaneous ne,:rosis.
KF.FEKF,NCES .\r.nengol. R.. More. [. X. ( h u . J. ( 1989) Heparin-induced skin ncc’rosis. thrornbocytopenia and pulmonary thrornboembolism. I’resentation of two cases. Mediririn Clinicn (Rurcriona), 9.3, (39% ‘-01 , Bell. \.\’.K. & Royal. R.M. ( 1980) Heparin-associated thrombocytopenia: a comparison of three heparin preparations. New England piirtrd of ,lltdi(.irw. 303, 902-904. (-raig. A..Taherner. DA., Fisher. A.H.. Foster. 1I.N. &Mitra,1. (1990) .rype I protein S deficiency and skin necrosis. Posfgruduutp Mcdicul ) o u t - t r d , 66. 389-391. G d a l . H.C. ( 1989) Heparin-induced thronibocytopenia. Heparin. ( ’ l i t 7 r t i i r a l mid Biological Properties. Clinical Applications (ed. by D. A. I,ane and II. Lindahll. chap. 2 5 . p. 542. Edward Arnold. Oxford. Slanoharan. A. ( 1992) Heparin-induced skin reaction with low inolecular-weight heparin. Europenrr joirrnnl of Huwinfohjy, 48. 2?4. Shdnott‘. J.G. & lle 131asio.G. ( 1 970) Prevention of fatal post-operative throinboenibolism by heparin prophylaxis. Lurrcet. ii, 1006. \!‘hire, K,\t’,, John. R.S. & Kichard. E.N. ( 1979) Thrombotic roruplication of heparin therapy including six cases of heparin induced skin necrosis. Arirmls oj’Snrgery, 190, 595-598.
