Search

Venous thromboembolism [TE] is a multifactorial disease and protein C deficiency [PCD] constitutes a major risk factor. In the present study the prevalence of PCD and the clinical presentation at TE onset, including neonatal purpura fulminans, in a cohort of children are reported. In 367 unselected children (0·1-19 years) recruited between July 1996 and December 2013, a comprehensive thrombophilia screening was performed along with recording of anamnestic data. Twenty-five of 338 children (7·4%) had PCD. Mean age at first TE onset was 10 years (range 0·1-18). Leading thromboembolic manifestations were neonatal purpura fulminans (n = 5), TE of cerebral veins (n = 3), stroke (n = 2) deep veinthrombosis (DVT) of the leg (n = 10), DVT & pulmonary embolism (n = 2) and DVT & pelvic veins (n = 3). Concomitant risk factors for TE were identified in 12 patients, whereas 13 children spontaneously developed TE. A positive family history of DVT was found in 10 children. In this unselected cohort of paediatric patients with symptomatic TE the overall prevalence of PCD was 7·4%; 1·5% presented with neonatal purpura fulminans. Given its clinical implication for patients and family members, thrombophilia testing should be performed and the benefit of medical or educational interventions should be evaluated in this high-risk population., (© 2014 John Wiley & Sons Ltd.)

Systemic embolism in childhood is rare but often disastrous. Most often the concomitant occurrence of more than one prothrombotic factor is responsible for the acute event. We report on a child in whom an intracardiac thrombus embolized into the descending aorta resulting in subtotal occlusion. Causative for thrombus formation was an idiopathic ventricular tachycardia and a heterozygous activated protein C resistance, both previously unknown. Immediate surgical thrombectomy was successful without sequelae. Antithrombotic and antiarrhythmispioproptylactic treatment was started afterwards. We suggest that in cases of longstanding or repeated tachycardia and in children after thromboembolic events diagnostic work-up for thrombophilia should be undertaken.

The objective of this paper was to assess the risk of thrombosis in users of oral contraceptives. Furthermore, the sensitivity, specificity and predictive values of potential screening tests for the prediction of thromboembolic complications in users of oral contraceptives were calculated for the approximately six million German pill users. Despite high specificity, the predictive values of a positive family history, or evidence of either antithrombin III, protein C or protein S deficiency or resistance to activated protein C, are low due to the very low absolute risk of thrombosis among pill users. More than half of the 840 annual cases would pass the screening protocol undetected. A two-step screening protocol is suggested using family history as a selection criterion (thus reducing the need for laboratory screening by 85%) for laboratory investigation of activated protein C sensitivity and deficiencies of antithrombin III, protein C or protein S. Genotyping for factor V Leiden mutation is useful in cases with equivocal activated protein C sensitivities or to confirm a homozygous genotype.

A total of 2674 women were recruited to participate in a multicenter oral contraceptive (OC) study on hemostasis. At baseline, protein S activity less than 60% of normal values was found in two volunteers (0.75 per 1000) and the antithrombin III activity was less than 60% of normal values in three volunteers (1.1 per 1000). All measurements were confirmed by a second assessment. In contrast, of the 28 women presenting with protein C levels less than 60% of normal values, only six were confirmed (2.3 per 1000). Of these, one was also protein S-deficient. Seven women could not be studied twice and 15 were false-low according to their normal control values. These data suggest that routine screening of the hemostatic system may reveal findings suggestive of inhibitor deficiencies in as many as 3.75 per 1000 of apparently healthy candidates for OCs. However, our data also demonstrate that unselected screening is compromised by a considerable rate of false-positive results and cannot generally be recommended. However, screening of coagulation inhibitors is feasible in women with a family history of thromboembolic disease.

The factor V Leiden variant, responsible for the phenomenon of activated protein C resistance, was found to be less frequent among British (0.06) and Swedish/Danish (0.15) protein C deficiency patients than previously reported in a Dutch study (0.19). In the Swedish population, a significantly increased frequency of the factor V Leiden allele was apparent in protein C deficiency patients as compared to healthy controls. However, this was not found in the British population. Coinheritance of the factor V Leiden variant is therefore unlikely to be the sole determinant of whether a person with protein C deficiency will come to clinical attention. Nevertheless, when patient data were analysed by type of protein C deficiency, it was noted that the frequency of the factor V Leiden variant was 2.8-fold higher in type II patients compared to type I patients. A possible explanation of this disparity is discussed.

A novel homozygous GTG-->GCG (Val 325-->Ala) substitution was detected in the protein C gene of a newborn causing severe purpura fulminans post partum. In the consanguineous parents and two further infants a heterozygous type 1 protein C deficiency was found. Up to now the heterozygous individuals are clinically unaffected. The mutation co-segregates with the protein C deficiency state. It creates a restriction enzyme (Sac II) cleavage site.