Deficiencies of coagulation factors other than factor VIII and factor IX that cause bleeding disorders are inherited as autosomal recessive traits and are rare, with prevalences in the general population varying between 1 in 500 000 and 1 in 2 million for the homozygous forms. As a consequence of the rarity of these deficiencies, the type and severity of bleeding symptoms, the underlying molecular defects, and the actual management of bleeding episodes are not as well established as for hemophilia A and B. We investigated more than 1000 patients with recessively inherited coagulation disorders from Italy and Iran, a country with a high rate of recessive diseases due to the custom of consanguineous marriages. Based upon this experience, this article reviews the genetic basis, prevalent clinical manifestations, and management of these disorders. The steps and actions necessary to improve the condition of these often neglected patients are outlined.

The most common medical cause of major blood loss is surgery, particularly cardiovascular procedures, liver transplantation and hepatic resection, and major orthopedic procedures. Excessive blood loss may also occur for other reasons, such as trauma. This article reviews the benefits of hemostatic drugs and considers the associated risk of adverse events, particularly thrombotic complications.

Over the past forty years the availability of coagulation factor replacement therapy has greatly contributed to the improved care of people with hemophilia. Following the blood-borne viral infections in the late 1970s and early 1980, caused by coagulation factor concentrates manufactured using non-virally inactivated pooled plasma, the need for safer treatment became crucial to the hemophilia community. The introduction of virus inactivated plasma-derived coagulation factors and then of recombinant products has revolutionized the care of these people. These therapeutic weapons have improved their quality of life and that of their families and permitted home treatment, i.e., factor replacement therapy at regular intervals in order to prevent both bleeding and the resultant joint damage (i.e. primary prophylaxis). Accordingly, a near normal lifestyle and life-expectancy have been achieved. The main current problem in hemophilia is the onset of alloantibodies inactivating the infused coagulation factor, even though immune tolerance regimens based on long-term daily injections of large dosages of coagulation factors are able to eradicate inhibitors in approximately two-thirds of affected patients. In addition availability of products that bypass the intrinsic coagulation defects have dramatically improved the management of this complication. The major challenges of current treatment regimens, such the short half life of hemophilia therapeutics with need for frequent intravenous injections, encourage the current efforts to produce coagulation factors with more prolonged bioavailability. Finally, intensive research is devoted to gene transfer therapy, the only way to ultimately obtain cure in hemophilia.

The diagnosis of an underlying chronic myeloproliferative disorder (CMPD) is often problematic in patients with primary extrahepatic portal vein obstruction (EHPVO) or Budd-Chiari syndrome (BCS); indeed, conventional clinical and hematological parameters usually yield insufficient information. To assess the diagnostic contribution of the gain-of-function mutation V617F of the JAK2 gene, 93 patients with EHPVO or BCS were investigated. JAK2 V617F was identified in 35.6% of 73 patients with EHPVO and in 40% of 20 patients with BCS. Taking the JAK2 mutation as a test with the highest positive predictive value for the diagnosis of CMPD, conventional clinical-hematological parameters had a sensitivity for CMPD lower than 48%. Bone marrow (BM) histology provided a diagnosis of CMPD in 41/74 (55.4%) patients, with a sensitivity of 93.5%. Clonality of hematopoiesis as assessed by granulocyte X-chromosome inactivation was present in 65.1% of 43 informative female patients, with a sensitivity of 86.6%. By resolving the sensitivity bias of the JAK2 mutation with the results of BM histology and clonality assay, CMPD was diagnosed in 53% of patients with EHPVO or BCS. In conclusion , CMPD is the major cause of primary EHPVO or BCS. JAK2 V617F is a very reliable and noninvasive molecular marker for CMPD and should be used as a first test for diagnosis.

In persons with hemophilia, life expectancy is now approaching that of the general male population, at least in countries that can afford regular replacement therapy with coagulation factor concentrates. The new challenges for comprehensive treatment centers are thus to provide optimal health care for this aging population of patients, who often present not only with the comorbidities typically associated with hemophilia (arthropathy, chronic pain, blood-borne infections), but also with common age-related illnesses such as cardiovascular disease and cancer. There are no evidence-based guidelines for the management of these conditions, which often require drugs that interfere with hemostasis, enhance the bleeding tendency, and warrant more intensive replacement therapy. At the moment, elderly patients with hemophilia affected by other diseases should be managed like their age-group peers without hemophilia, provided replacement therapy is tailored to the heightened risk of bleeding associated with the need for invasive procedures and drugs that further compromise the deranged hemostasis. More detailed advice is provided on the schedules of replacement therapy needed to tackle cardiovascular diseases, such as acute coronary syndromes and nonvalvular atrial fibrillation, because these conditions will become more and more frequent challenges for the comprehensive treatment centers.

Summary. Background and objectives: A plasma‐derived von Willebrand factor (VWF) concentrate with low factor VIII (FVIII) content was specifically developed to treat von Willebrand disease (VWD). Efficacy and safety were investigated by merging the results of two comparable protocols conducted prospectively in 5 European and 12 French centers. Methods and results: Fifty patients with clinically severe VWD (72% had VWF ristocetin cofactor activity less than 10 IU dL^–1 and 46% had FVIII < 20 IU dL^–1) were treated with the concentrate as the only therapy, except for clinical situations requiring a priming dose of FVIII to rapidly correct an intrinsic coagulation defect. A total of 139 spontaneous bleeding episodes were treated; only 53 (38%) needed a concomitant FVIII dose. Outcome was excellent or good in 89% of the episodes. Forty‐four patients underwent 108 surgical or invasive procedures. Outcome was excellent or good in 95 scheduled procedures (only VWF was infused) and 13 emergency procedures (a priming FVIII dose was co‐administered with the first VWF infusion). There were no thrombotic complications and none of the 18 patients with type 3 VWD developed anti‐VWF or anti‐FVIII antibodies. Conclusions. This concentrate safely and effectively provides hemostasis in patients with clinically severe VWD.