Prevalence of Bleeding Symptoms among Adolescents and Young Adults in the Capital City of Saudi Arabia

Background.Bleeding disorders vary in prevalence. While some are rare, some can be common in both sexes. Most bleeding disorders manifest as chronic bleeding tendencies or as an increase in bleeding during surgical procedures or trauma. The consequences of bleeding can be as simple as iron deficiency or catastrophic, resulting in severe morbidity and mortality. Bleeding disorders typically affect both sexes except hemophilia A and B, which mainly affects males.Method.We conducted a questionnaire-based survey among adolescents and young adults (1901[49%]boys, 1980[51%]girls) in Riyadh city regarding bleeding symptoms. Of these, 1849 (47.6%) responded “Yes/Positive” for at least one question about the bleeding symptoms.Results.The most common bleeding symptom was epistaxis (19.7% of the sample population) detected in Phase I of the study. A tandem survey was conducted among 525 adolescents who had responded “Yes/Positive” to any one of the questions inquiring about bleeding symptoms.Conclusion.In this study, we report for the first time the prevalence of bleeding symptoms in a representative sample of Saudi adolescents and young adults.

Bleeding symptoms at disease presentation and prediction of ensuing bleeding in inherited FVII deficiency

SummaryIndividuals with inherited factor VII (FVII) deficiency display bleeding phenotypes ranging from mild to severe, with 30% of patients having always been asymptomatic (non-bleeding). In 626 FVII-deficient individuals, by analysing data from the International Factor VII (IF7) Registry and the Seven Treatment Evaluation Registry (STER), we determined whether bleeding type at disease presentation and FVII coagulant activity (FVIIc) predict ensuing bleeds. At disease presentation/diagnosis, 272 (43.5%) individuals were non-bleeding, 277 (44.2%) had minor bleeds, and 77 (12.3%) had major bleeds. During a median nine-year index period (IP) observation, 87.9% of non-bleeding individuals at presentation remained asymptomatic, 75.1% of minor-bleeders had new minor bleeds, and 83.1% of major-bleeders experienced new major bleeds. After adjusting for FVIIc levels and other clinical and demographic variables, the relative risk (RR) for ensuing bleedings during the IP was 6.02 (p <0.001) and 5.87 (p <0.001) in individuals presenting with major and minor bleeds, respectively. Conversely, compared to non-bleeding individuals, a 10.95 (p = 0.001) and 28.21 (p <0.001) RR for major bleedings during the IP was found in those with minor and with major bleeds at presentation, respectively. In conclusion, in FVII deficiency, the first major bleeding symptom is an independent predictor of the risk of subsequent major bleeds.

At Disease Presentation, Severity of the Bleeding Symptom Predicts the Following Bleeds in Patients with FVII Deficiency

Abstract 30 Background: Inherited Factor VII (FVII) deficiency is the most common of the “rare” autosomal recessive bleeding disorders. Affected individuals display a wide range of clinical phenotypes and treatment demand may vary from prophylaxis to the need of rare or no replacement at all. As a matter of fact, it would be important to individualize the optimal and safest management with reference to the risk of bleeding. Objective: In a large number of subjects with FVII deficiency, we evaluated whether the type of symptom at disease presentation could help to predict further symptoms during the “Observation Period” (OP). Methods: Appropriate information in subjects with FVII deficiency, collected in the multicentre STER and IF7SG Registries, were employed. OP= time elapsed between the date of disease-presentation symptom and that of enrolment into the registry. Data for this analysis were complete for 687 individuals. Results: At diagnosis, among the 687 subjects (356 [51.8%] females, 331 [48.2%] males, mean age 29.6±19.63 yrs), 272 (39.6%) were asymptomatic; of the symptomatic individuals, 338 (49.2%) displayed a mild “Platelet- Like” (PL) bleeding defect (i.e. muco-cutaneous bleedings) and 77 (11.2%) had a severe, “Hemophilia-Like” (HL), phenotype. Mean age at diagnosis for the asymptomatic individuals was 23.8±18.8; mean ages at disease presentation were 10.54 ±11.8 for the PL, and 5.5 ±12.3 for the HL individuals ( p for trend= 0.000). FVII activity (FVIIc) was: females 17.53±19.68%, males 18.58±17.50% (p=0.460), overall: 18.04 ±18,66%. Of the 338 individuals with a PL-disorder, 268 (79.3%) had new muco-cutaneous bleedings; 51 (15.1%) developed severe bleedings, and 12 (4%) did not develop any subsequent bleed. Among the patients (n=77) with a HL-disorder, 38 (49.4%) experienced new severe bleeds, 34 (44.2%) developed mucosal bleedings, and only 5 (6.5%) had no further bleeds. Among those asymptomatic at diagnosis (n=272), 237 (87.1%) remained asymptomatic, while 35 (12.9%) developed only muco-cutaneous bleedings. Thus, 87.1% of the asymptomatic individual at diagnosis remained so, 79.3% of those with a platelet-like disorder at diagnosis displayed the same type of bleeding and, finally, 50% of those with severe bleedings at diagnosis had, again, severe bleeds. FVIIc helped to refine clinical information. Asymptomatic individuals at diagnosis that subsequently developed muco-cutaneous bleedings, had FVIIc similar to that of individuals with the same mild bleeds at onset (∼15–20%). FVIIc of individuals with PL-disorder at diagnosis who subsequently experienced a life- and limb-threatening bleeding episode, were as low (<5%) as those of individuals that had a severe phenotype at disease presentation. Regardless whether documented at diagnosis or during the OP, severe bleeding was invariably associated with FVIIc <5%. At diagnosis, the latter levels were found in 88.3% of individuals with severe symptoms, in 57.8% of those with muco-cutaneous bleedings and in 14.7% of asymptomatic individuals. Conclusions: In Factor VII deficiency, three clinical phenotypes can be identified: 1. the most prevalent cohort experience muco-cutaneous bleeding (PL-disorder); 2. Ten–15% of patients exhibit potentially life- or limb-threatening hemorrhages, such as hemartroses, central nervous system (CNS) or gastrointestinal (GI), a phenotype that may be as severe or more severe than that in hemophilia, and 3. about 1/3 of cases are asymptomatic and tend to remain so. Bleeding symptom at disease presentation predicts the subsequently developed bleeding phenotype. FVIIc levels refine such clinical prediction and help to identify individuals that call for early prophylaxis or on demand treatment. Disclosures: No relevant conflicts of interest to declare.

Thromboelastometry in Patients Receiving Platelet Transfusion after Chemotherapy.

Prophylactic platelet transfusion is frequently administered to reduce the risk of hemorrhage in patients undergoing chemotherapy for leukemia or cancer. A platelet count of 10 or 20x109 L−1 is often used as an occasion for platelet transfusion. In clinical studies, the bleeding risk was similar using either threshold (Rebulla, NEJM1997; 337:1870, Wand, Blood1998; 91:3601). Moreover, serious bleeding events were not related to the patients’ platelet count. Thromboelastometry with ROTEM® Whole-Blood Coagulation Analyzer (Pentapharm, Munich, Germany) is a method that may provide a better estimate of the risk of hemorrhage because it also depends on platelet function and plasma coagulation. We therefore performed a pilot study in 13 adult patients receiving prophylactic platelet transfusion after chemotherapy for leukemia or lymphoma. ROTEM® was performed using an ellagic acid based activating reagent (in-TEM®, Pentapharm). Clotting profiles were evaluated using the following thromboelastometric measures: clotting time (CT), clot formation time (CFT), and maximum clot firmness (MCF). The median platelet count before transfusion was 9x109 L−1 (range 1 to 20). CT was within the normal range in all patients (median 168 s, range 125–212, reference range 100–240). In contrast, a prolonged CFT (median 139 s, range 51–4526, reference range 30–110) and reduced MCF (median 34 mm, range 19–54, reference range 50–72) was recorded. Correlation between platelet count and CFT (R=−0.41, Spearman) or MCF (R=+0.48) was weak and not statistically significant. 15 min after platelet transfusion, there was an increase in platelet count (median 39x109 L−1, range 23–48) and a substantial improvement of CFT (median 99 s, range 44–332) and MCF (median 49 mm, range 40–64). Changes in thromboelastometric measures were due to platelet transfusion as the addition of cytochalasin D (fib-TEM®, Pentapharm) resulted in identical profiles before and after transfusion. Changes in platelet count correlated with changes in MCF (R=+0.73, P<0.01), but not CFT (R=−0.40, P=0.17). Comparing patients who had a maximum of one mild bleeding symptom (n=9) with patients who experienced one severe or at least two mild bleeding symptoms (n=4), there was no difference in platelet counts (median 10 vs. 9x109 L−1, p=0.77). In contrast, there was a trend towards a shorter CFT (median 111 vs. 388 s, P=0.09) and higher MCF (median 39 vs. 29.5 mm, P=0.09) in the group of non-bleeding patients. In summary, ROTEM® seems to be a sensitive method to detect hemostatic changes in patients with severe thrombocytopenia receiving platelet transfusion and to identify thrombocytopenic patients with an increased bleeding risk. Therefore, further studies to evaluate ROTEM® as a means to estimate the bleeding risk in thrombocytopenic patients are warranted.