| A 35 year old woman presented with acute myocardial infarction without any of the usual risk factors: she had never smoked; she had normal blood pressure; she did not have diabetes; plasma concentrations of total cholesterol and high and low density lipoprotein cholesterol, fibrinogen, homocysteine, and Lp(a) lipoprotein were normal. She was not taking oral contraceptives or any other medication. coronary angiography showed occlusion of the left anterior descending coronary artery but no evidence of arteriosclerosis. Medical history disclosed a previous leg vein thrombosis with pulmonary embolism. Coagulation analysis revealed protein c deficiency. The recognition of protein c deficiency as a risk factor for myocardial infarction is important as anticoagulation prevents further thrombotic events, whereas inhibitors of platelet aggregation are ineffective. ( info) |
| Septic arthritis and osteomyelitis in children is seldom accompanied by calf vein thrombosis and rarely by atrial thrombosis. We report the case of an 11-year, 5-month-old boy with septic arthritis and osteomyelitis of the sacroiliac region who developed deep venous thrombosis, in addition to life-threatening right atrial thrombosis. After an intensive hematologic investigation, a hereditary protein c deficiency was revealed. The association of venous thrombosis with septic arthritis or osteomyelitis should raise the possibility of the presence of protein c deficiency. ( info) |
3/265. Long-term management of homozygous protein c deficiency: replacement therapy with subcutaneous purified protein C concentrate. We present the case of a full-term newborn in whom purpura fulminans developed shortly after birth. A diagnosis of homozygous protein c deficiency was established based upon undetectable plasma protein C activity and antigenemia in the newborn infant, and was later confirmed by protein C gene analysis. Specific replacement therapy with intravenous protein C concentrate was started 9 days after birth. This rapidly led to the complete regression of cutaneous lesions and consumption coagulopathy. After stabilization, oral anticoagulation was initiated in association with prophylactic treatment with intravenous protein C concentrate. However, oral anticoagulation was finally abandoned as the patient presented several thrombotic and hemorrhagic episodes clearly related to difficulties with anticoagulation. Due to the hazards related to prolonged venous access, we are currently using subcutaneous infusion of protein C concentrate for the long-term management of this condition, with satisfactory results. ( info) |
4/265. Ophthalmic manifestation of congenital protein c deficiency. Under normal conditions activated protein C is a natural anticoagulant that cleaves 2 activated coagulation factors, factor va and factor viiia, thereby inhibiting the conversion of factor X to factor xa and of prothrombin to thrombin. Additionally, activated protein C enhances tissue-plasminogen activator-mediated fibrinolysis by inhibition of plasminogen activator inhibitor-1. This results in an increase in circulatory plasminogen activator levels. protein c deficiency, a genetic or acquired thrombophilic abnormality, has been demonstrated to predispose to episodes of potentially blinding and lethal thromboembolic events. Heterozygous-deficient subjects usually remain asymptomatic until adolescence or adulthood. In homozygous-deficient patients, protein C activity is usually less than 1% (reference range, 70%-140%), resulting in thromboembolism as early as in the neonatal period. The major clinical symptoms in affected newborn infants have been purpura fulminans, vitreous hemorrhage, and central nervous system thrombosis. The age of onset of the first symptoms has ranged from a few hours to 2 weeks after birth, usually after an uncomplicated full-term pregnancy and delivery. In contrast to the genetic form, acquired neonatal protein c deficiency occurs particularly in ill preterm babies. Typical complications of prematurity such as respiratory distress syndrome, necrotizing enterocolitis, and neonatal sepsis may also be present. In the medical literature, there are only a few reports of homozygous protein c deficiency in neonates. We present 2 cases of homozygous protein c deficiency with ocular and extraocular manifestation. ( info) |
| An 83-year-old man had gradually worsening abdominal pain and vomiting. laparotomy revealed segmental intestinal infarction resulting from thrombosis in the superior mesenteric vein. Necrosed intestine was resected and anastomosis was performed successfully. The patient was anticoagulated with intravenous heparin and nafamostat mesilate followed by oral aspirin. He recovered rapidly. Blood chemistry revealed protein c deficiency, while protein S and antithrombin iii levels were normal. Laboratory evaluation of these proteins may help define the cause of mesenteric venous thrombosis. ( info) |
6/265. Inherited protein c deficiency, protein s deficiency and hyperhomocysteinaemia in a patient with hereditary spherocytosis. We report a family with hereditary spherocytosis in whom there is, in addition, a cluster of genetic predispositions to thrombosis. Although inherited prothrombotic abnormalities are prevalent in the general population, the likelihood of this combination of abnormalities being found in a single family is extremely low. The management of such high risk individuals is discussed. ( info) |
7/265. A novel splice acceptor site mutation which produces multiple splicing abnormalities resulting in protein s deficiency type I. In an attempt to explore the molecular mechanisms for protein s deficiency, a patient with such a deficiency was examined at the dna, rna and protein levels. Nucleotide analyses revealed that the proband, the mother and the grandmother had a G-->C substitution in the invariant AG dinucleotide at the splicing acceptor site of intron A/exon 2. This patient was heterozygous for this substitution and the mutant allele was inherited from the proband's mother and grandmother. reverse transcription-polymerase chain reaction analysis demonstrated several kinds of splicing abnormalities such as exon skipping and cryptic splicing, in addition to correct splicing. Semiquantitation of mRNA for the protein S gene revealed that the amount of the proband's mRNA was reduced to 60% of normal. Thus, this mutation impaired the normal processing of mRNA for the protein S gene, resulting in the subject's severe protein s deficiency. ( info) |
8/265. Acquired protein c deficiency following cisplatinum-navelbine administration for locally advanced breast cancer. Case report. Thromboembolic events have recently been reported following diverse regimens of chemotherapy for breast cancer. This is a report of a 39-year-old woman, a diagnosed case of locally advanced breast cancer, who received many regimens of chemotherapy. She presented with deep venous thrombosis 2 months after starting the cisplatinum-navelbine regimen. protein c deficiency was the only abnormal coagulation test that normalized after cessation of chemotherapy. ( info) |
9/265. stroke after zoster ophthalmicus in a 12-year-old girl with protein c deficiency. A 12-year-old girl who had zoster ophthalmicus 10 months earlier presented with hemiparesis and corresponding basal ganglionic infarction related to middle cerebral artery branch thrombosis ipsilateral to the zoster. Hematologic evaluation disclosed protein c deficiency. This represents the first zoster-associated stroke reported in childhood associated with protein c deficiency, with extension of the latency period between zoster and infarction, previously reported to be 6 months. ( info) |
| A 42-year-old male presented with right-sided weakness, dysphasia and seizures while climbing the French Alps at an approximate altitude of 3,000 m. Imaging studies were consistent with superior sagittal sinus thrombosis with hemorrhage. Laboratory testing for thrombophilic states, 18 days after presentation at our hospital, showed a low protein C level (0.32 U/ml, normal 0.80-1.60 U/ml). A family member was also found to have protein c deficiency without a history of thrombosis. The patient gradually improved and was discharged on warfarin and valproic acid. This is the first reported case of cerebral venous thrombosis in a patient with congenital protein c deficiency who ascended to high altitude. We postulate that the ascent to high altitude represented an additional prothrombotic risk factor to the congenital protein c deficiency leading to cerebral thrombosis. ( info) |