Ehlers-Danlos syndrome (EDS) is a group of inherited connective tissue disorders caused by collagen synthesis defects. Several hemostatic abnormalities have been described in EDS patients that increase the bleeding tendencies of these patients. This case report illustrates a patient with an unusual presentation of a patient with type IV EDS, platelet δ-storage pool disease and factor V Leiden mutation. Young woman having previous bilateral deep vein thrombosis and pulmonary emboli coexisting with ruptured splenic aneurysm and multiple other aneurysms now presented with myocardial infarction. Presence of factor V Leiden mutation raises the possibility that the infarct was due to acute coronary thrombosis, although coronary artery aneurysm and dissection with myocardial infarction is known to occur in vascular type EDS. This is the first report in the medical literature of factor V Leiden mutation in an EDS patient which made the management of our patient challenging with propensity to both bleeding and clotting.

Easy bruising and bleeding are not only characteristic manifestations of clotting and platelet disorders, they are also prominent features in some heritable collagen disorders, such as the Ehlers-Danlos syndromes (EDS). The EDS comprise a heterogeneous group of connective tissue diseases sharing clinical manifestations in skin, ligaments and joints, blood vessels and internal organs. Most EDS subtypes are caused by mutations in genes encoding the fibrillar collagens type I, III and V, or in genes coding for enzymes involved in the post-translational modification of these collagens. Easy bruising is, to a variable degree, present in all subtypes of EDS, and is because of fragility of the capillaries and the perivascular connective tissues. Vascular fragility affecting medium-sized and large arteries and veins is typically observed in the vascular subtype of EDS, caused by a molecular defect in collagen type III, an important constituent of blood vessel walls and hollow organs. Extensive bruising, spontaneous arterial rupture, leading to severe internal bleeding or premature death, and rupture of hollow organs, such as the intestine or the gravid uterus are predominant features of this subtype. Haematological studies including evaluation of clotting factors, platelet aggregation and bleeding time are usually normal in patients with EDS, except for the Hess test (Rumple-Leede test), which may be abnormal, indicating capillary fragility. In some forms of EDS confirmation of the clinical diagnosis and subtype is possible with biochemical and molecular studies.

Haemostatis has not previously been studied in patients with neurofibromatosis 1 (NF-1), despite case reports of an association with von Willebrand disease and reported excessive bleeding in those undergoing surgery for neurofibromas. Platelets from NF-1 patients (n = 28) were tested for aggregation and ATP release with agonists including ADP, arachidonic acid, thrombin and collagen. Mepacrine staining of platelets and three different assays for von Willebrand factor (VWF) were also performed. In response to collagen as the platelet agonist, tested at both 2 and 1 micrograms/ml, NF-1 patients had an attenuated rate of aggregation (P < 0.007), aggregation lag phase (P < 0.005) and ATP release (P < 0.045), as well as requiring higher collagen concentrations to attain threshold aggregation response (P = 0.041). Normal platelets resuspended in selected NF-1 plasma exhibited significantly reduced platelet aggregation and release compared to controls, which was not corrected by mixing 1:1 with normal plasma. Collagen binding activity was reduced in NF-1 patients compared with controls (127% v 161%, P = 0.05). As a group, patients with NF-1 display defective platelet function characterized by in vitro evidence of impaired responsiveness to collagen. It is suggested that a plasma factor, present in a significant proportion of NF-1 patients, may interfere with the ability of collagen to interact with other proteins such as von Willebrand factor and the platelet collagen receptor.

Fifty-one patients with Ehlers-Danlos syndrome were investigated for abnormalities of platelets and coagulation. Thirty-eight were examined prospectively and 13 retrospectively. A bleeding history was taken from all patients; only four (8%) gave no history of a bruising or bleeding tendency. Nine patients (18%) had significant haemostatic abnormalities of whom four (8%) had a platelet release defect, three (6%) had a factor XI deficiency and two (4%) had a factor XIII deficiency. Additionally 16 patients (31%) had mild abnormalities of uncertain significance of whom four (8%) had prolonged bleeding times (three in association with platelet aggregation abnormalities), 13 (26%) had platelet aggregation abnormalities and two had a positive Hess test. Twenty-four patients (47%) had normal tests for haemostasis of whom 20 (39%) had a bleeding diathesis and four (8%) had no such tendency. Results were analysed according to the type of Ehlers-Danlos syndrome, but there was no pattern to the abnormalities. The high frequency of a bleeding tendency in Ehlers-Danlos patients with normal tests for haemostasis (83%) supports the conventional explanation for this clinical feature, that defects in the structural integrity of skin and blood vessels lead to easy bruising.

A case of the Ehlers-Danlos syndrome associated with cleft lip and palate is presented. This is the first reported case with cleft lip and palate. The cleft palate in our case was successfully repaired by palatoplasty (push-back operation). The aetiology, clinical features and surgical problems of this syndrome are discussed.

The clinical and laboratory findings in a patient with severe gastro-intestinal bleeding and the Ehlers-Danlos syndrome are described. Coagulation studies and a lack of history of previous haemorrhage were consistent with a diagnosis of acquired von Willebrand's syndrome. His response to treatment with blood transfusion, Factor VIII, cimetidine, tranexamic acid and cyclophosphamide is described. Family studies revealed other members with Ehlers-Danlos syndrome but normal coagulation.

Death from arterial bleeding or gastrointestinal perforation has previously been reported in more than 15 patients with the Ehlers-Danlos syndrome. On a basis of 100 personally examined patients and a review of published accounts, these events seem particularly likely to occur in two distinct and recognizable forms (the gravis and the ecchymotic forms) of the syndrome.