646
Journal of the Royal Society of Medicine Volume 83 October 1990
Case reports
Cutaneous necrosis associated with protein S deficiency
Case presented to Section of Dermatology 16 February 1989
C M Proby BA MRCP' A Chitolie BSc FIMLS2 D H Bevan MRCPmRCPath2 P S Mortimer MB MRcP Departments of 'Dermatology and 2Haematology, St George's Hospital, London SW17 OQT Keywords: cutaneous necrosis; protein S deficiency; lupus anticoagulant; arterial disease
Skin necrosis, arising from abnormality in the anticoagulant arm of the coagulation cascade, is increasingly recognized in the antiphospholipid antibody syndrome, coumnarin necrosis and protein C deficiency',. Protein S deficiency in association with coumarin therapy has recently received similar attention3. We report a case of skin necrosis associated with protein S deficiency and lupus anticoagulant. Thiscombination may lead to cutaneous infarction without coumarin.
Figure 1. Cutaneous infarction on right thigh
Case report A 67-year-old woman underwent left above knee and right below knee amputations, in 1980 and 1982 respectively, for persistent leg pain at rest. She was a nonsmoker with no known risk factors for arterial disease. Subsequently she remained well on no medication. In October 1988 she presented with a 3-month history of spontaneous non-healing ulceration of her distal right stump. When conservative management failed, she was admitted for surgical debridement and revision of the fight stump. Heparin 5000 iu subcutaneously three times a day was given perioperatively. Three days later she developed reticulate areas of cutaneous necrosis on both thighs with firm subcutaneous swellings and, in places, frank eschar formation (Figure 1). Laboratory investigations, off all anticoagulants, demonstrated a lupus anticoagulant plus protein C and S deficiencies. Serial coagulation studies are ummarie in Table 1. Skin biopsies from affected areas showed intravascular thrombus in dermal and subcutaneous vessels with associated areas of full thickness infarction. There was
no vasculitis in any section. Eythrocyte s ntationrate was elevated at 120 mm/h but all other investigations pertaining to vasculitis or thrombotic states were normal or negative. She was stabilized on warfarin under heparin cover. Despite initial improvement, further areas of cutaneous necrosis developed on both thighs. Coagulation studies, repeated while on warfarin, found an international normalized ratio (NR) of 2.1, vitamin K-dependent procoagulant factors II, VI[, IX and X all mildly reduced consistent with anticagulation, protein C 57 iu/dl (normal >65 iu/dl) and free protein S 25% pooled normal plasma (normal range >65%). Her warfarin doses were increased to stabilize the INR between 2.5 and 3.5. Therafter, all cutaneous lesions steadily resolved and have remained healed some 8 months later. Subsequent coagulation studies (Table 1) show consistently depleted free protein S levels (polyethylene glycol-treated to dissociate bound protein S) at around 25%, while protein C levels of around 50 iu/dl are unremarkable in someone on warfarin. A lupus antigulant remains present, as evidenced by both an elevated dilute Russell viper venom ratio and an elevated tissue thromboplastin inhibitor test ratio.
Table 1. Serial coagulation studies
Date
November 1988 January 1989 March 1989 July 1989 August 1989
Dilute Russell AnticoViper agulation Venom (warfarin) ratio none
Tissue thromboplastin inhibitor test ratio
1.6
1.1
2.0
1.8
INR 2.1 INR 2.4
INR 2.8
Procoagulant factors
Protein S
(immunological) Protein C
VII
IX
X
92 36
78 70
150 50
103 16
20
35
30
12
II
(iu/dl)
(chromogenic) (iu/dl) 24 57 51 45
Total (%) 130 120 135 120
Free (%) 21 25 21 20 20 percentage
pooled Normal ranges
Journal of the Royal Society of Medicine Volume 83 October 1990
Case reports
Cutaneous necrosis associated with protein S deficiency
Case presented to Section of Dermatology 16 February 1989
C M Proby BA MRCP' A Chitolie BSc FIMLS2 D H Bevan MRCPmRCPath2 P S Mortimer MB MRcP Departments of 'Dermatology and 2Haematology, St George's Hospital, London SW17 OQT Keywords: cutaneous necrosis; protein S deficiency; lupus anticoagulant; arterial disease
Skin necrosis, arising from abnormality in the anticoagulant arm of the coagulation cascade, is increasingly recognized in the antiphospholipid antibody syndrome, coumnarin necrosis and protein C deficiency',. Protein S deficiency in association with coumarin therapy has recently received similar attention3. We report a case of skin necrosis associated with protein S deficiency and lupus anticoagulant. Thiscombination may lead to cutaneous infarction without coumarin.
Figure 1. Cutaneous infarction on right thigh
Case report A 67-year-old woman underwent left above knee and right below knee amputations, in 1980 and 1982 respectively, for persistent leg pain at rest. She was a nonsmoker with no known risk factors for arterial disease. Subsequently she remained well on no medication. In October 1988 she presented with a 3-month history of spontaneous non-healing ulceration of her distal right stump. When conservative management failed, she was admitted for surgical debridement and revision of the fight stump. Heparin 5000 iu subcutaneously three times a day was given perioperatively. Three days later she developed reticulate areas of cutaneous necrosis on both thighs with firm subcutaneous swellings and, in places, frank eschar formation (Figure 1). Laboratory investigations, off all anticoagulants, demonstrated a lupus anticoagulant plus protein C and S deficiencies. Serial coagulation studies are ummarie in Table 1. Skin biopsies from affected areas showed intravascular thrombus in dermal and subcutaneous vessels with associated areas of full thickness infarction. There was
no vasculitis in any section. Eythrocyte s ntationrate was elevated at 120 mm/h but all other investigations pertaining to vasculitis or thrombotic states were normal or negative. She was stabilized on warfarin under heparin cover. Despite initial improvement, further areas of cutaneous necrosis developed on both thighs. Coagulation studies, repeated while on warfarin, found an international normalized ratio (NR) of 2.1, vitamin K-dependent procoagulant factors II, VI[, IX and X all mildly reduced consistent with anticagulation, protein C 57 iu/dl (normal >65 iu/dl) and free protein S 25% pooled normal plasma (normal range >65%). Her warfarin doses were increased to stabilize the INR between 2.5 and 3.5. Therafter, all cutaneous lesions steadily resolved and have remained healed some 8 months later. Subsequent coagulation studies (Table 1) show consistently depleted free protein S levels (polyethylene glycol-treated to dissociate bound protein S) at around 25%, while protein C levels of around 50 iu/dl are unremarkable in someone on warfarin. A lupus antigulant remains present, as evidenced by both an elevated dilute Russell viper venom ratio and an elevated tissue thromboplastin inhibitor test ratio.
Table 1. Serial coagulation studies
Date
November 1988 January 1989 March 1989 July 1989 August 1989
Dilute Russell AnticoViper agulation Venom (warfarin) ratio none
Tissue thromboplastin inhibitor test ratio
1.6
1.1
2.0
1.8
INR 2.1 INR 2.4
INR 2.8
Procoagulant factors
Protein S
(immunological) Protein C
VII
IX
X
92 36
78 70
150 50
103 16
20
35
30
12
II
(iu/dl)
(chromogenic) (iu/dl) 24 57 51 45
Total (%) 130 120 135 120
Free (%) 21 25 21 20 20 percentage
pooled Normal ranges
