The longest life expectancy makes hemophiliacs susceptible to diseases not related to haemophilia and belonging to the general population as cerebro-cardiovascular pathologies and malignacies. Predictable is also that the younger patients, children and adolescents, suffer from disorders caused by well-being: obesity, metabolic syndrome, abnormal glucose tolerance.
In severe elderly hemophiliacs chronic arthropathy is the most frequent cause of falls and bone fractures aggravated by osteoporosis. These accidents imply a significant increase in major orthopedic surgery, particularly oriented to arthroplasty, including revisions of previously implanted prostheses. These interventions become more complex in hemophiliacs with inhibitors due to the increased bleeding risk and the costs they entail.
One of the emerging problems in major orthopedic surgery in elderly hemophiliacs is the risk of venous thromboembolism so far minimized.
The legitimate question arises whether venous thromboprophylaxis is mandatory in these cases. A scheme of venous thromboprophylaxis in hemophiliacs undergoing major orthopedic surgery suggests the administration of low molecular weight heparin subcutaneously 12-24 hours after intervention, continuing for at least 4 weeks or until mobilization. Venous thromboprophylaxis with elastic stockings and intermittent pneumatic compression is indicated in patients with inhibitor, early mobilization in arthroscopic procedures.
Literature reports that arterial hypertension is more prevalent in hemophiliacs than in males of the general population. It has been hypothesized that the phenomenon may be related to intensive replacement treatments, renal complications secondary to combined antiretroviral therapy or to repeated use of antifibrinolytics due to renal cortical necrosis.
Whether severe haemophilia protects against coronary ischemic events and atherosclerosis because of the congenital defect requires solid proofs. A lower incidence of mortality from cardiac ischemic events in hemophiliacs is reported than in the general male population, while atrial fibrillation appears to be as prevalent as in the non-haemophilic population: 3.4% in subjects over the age of 60. These data need specific recommendations on antithrombotic and anticoagulant treatments. Antithrombotic prophylaxis secondary to myocardial infarction with ASA 100 mg/day requires the anti-hemorrhagic protection with low doses of factor VIII/factor IX (FVIII/FIX) concentrates on alternate days. The use of non-medicated stents over medicated ones is preferable as it limits the association of ASA with clopidogrel or prasugrel to one month.
The blood levels (“trough level”) of the FVIII/FIX are specified below for antihemorrhagic prophylaxis associated with antithrombotic/anticoagulant therapies.
Attention must be kept to the risk of gastrointestinal hemorrhage always lurking with these specific treatments.
A dramatic reduction in mortality in HCV or HIV infection/coinfection is due to direct antiviral drugs for chronic hepatitis C and combination of antiretroviral treatment for HIV-infected persons. However, side effects have been observed secondary to the use of antiretroviral drugs such as metabolic syndrome, diabetes, nephrotic syndrome and cardiovascular diseases with a 26%/year increase in the relative risk of myocardial infarction.
In elderly hemophiliacs, attention is focused on the prevalence of malingnancies. As in the case of cardiovascular diseases, protection by the congenital defect has been hypothesized, for which the physiological state of anticoagulation would reduce tumor growth and implantation metastases. An Italian study showed that virus-related forms of cancer were significantly prevalent in severe hemophiliacs compared to moderate/mild ones, where related non-virus forms prevail (P = 0.0004). Furthermore the standard mortality rate was lower for the related non-virus cancer (SMR = 0.3), so that the mortality rate from virus-related cancer is higher in severe hemophiliacs. Supporting the above hypothesis, the mortality rate for non-virus related neoplastic forms decreases in severe hemophiliacs. Bleeding is described in chemotherapy (14%) and radiotherapy (19%).
It has been reported that the depressive state is more frequent in elderly hemophiliacs than in non-haemophilic males, which causes a worsening of the quality of life. Depressive state was also detected in elderly hemophilic with higher severity inhibitor compared to younger hemophilic with inhibitor.
A recent study “showed that obesity, hypertention and metabolic syndrome are frequent problems in young patients, especially in those over 18 years with arthropathy. Early prevention and management of overweight, obesity and their sequelae must be addressed in clinical practice in order to maximize the overall health of haemophiliacs. Therefore, assessment of cardiovascular and metabolic risk factors, beginning from early childhood, is crucial for this specific population.”.
The evaluation of comorbidities not strictly related to haemophilia requires particular attention in all age groups: from adolescence to adulthood and elderly age. Multispecialistic and integrated assistance to patients with haemophilia must include internists, geriatricians and general practitioners so that patients can be considered globally, focusing specific attention to the prescription of drugs.
Suggested readings
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