Rare diseases accompanied by bleeding disorders

Bleeding due to pathology of blood vessels

Bleeding may result from abnormalities of platelets, coagulation factors, and blood vessels. Vascular bleeding disorders are caused by pathology of the vascular wall and usually present with petechiae and purpura, but rarely cause serious blood loss. Bleeding may result from deficiency of vascular or perivascular collagen in Ehlers-Danlos syndrome, other rare hereditary connective tissue disorders (eg, pseudoxanthoma elasticum osteogenesis imperfecta, Marfan syndrome). Bleeding may be the main manifestation in scurvy or Henoch-Schonlein purpura, allergic vasculitides, which usually manifest in childhood. In vascular bleeding disorders, hemostasis tests usually remain within normal limits. The diagnosis is based on clinical manifestations.

[ 1 ], [ 2 ], [ 3 ]

Autosensitivity to red blood cells (Gardner-Diamond syndrome)

Red blood cell autosensitivity is a rare disorder occurring in women and is characterized by localized pain and painful ecchymosis, primarily affecting the extremities.

In women with autosensitization to red blood cells, intradermal injection of 0.1 ml of autologous red blood cells or red blood cell stroma may cause pain, swelling, and induration at the injection site. This result suggests that red blood cells that have infiltrated the tissues are involved in the pathogenesis of the lesion. However, most patients also have manifestations of a severe psychoneurotic syndrome. Moreover, psychogenic factors such as self-induced purpura may be associated with the pathogenesis of the syndrome in some patients. The diagnosis is based on examination of the site of intradermal injection of autoerythrocytes and the site of control injection (without red blood cells) 24 and 48 hours after injection. Lesions may complicate the interpretation of the test, so it is necessary to select injection sites that are difficult for the patient to access.

[ 4 ], [ 5 ], [ 6 ]

Dysproteinemias causing vascular hemorrhagic rash (purpura)

Amyloidosis causes amyloid deposition in the blood vessels of the skin and subcutaneous tissues, which can cause increased vascular fragility, leading to purpura. In some patients, amyloid adsorbs factor X, causing a deficiency, but this usually does not lead to bleeding. Periorbital hemorrhages or a hemorrhagic rash that develop in a patient after a mild blow in the absence of thrombocytopenia suggest the presence of amyloidosis.

Cryoglobulinemia is caused by immunoglobulins that precipitate when plasma cools as it passes through the skin and subcutaneous tissues of the extremities. Monoclonal immunoglobulins, such as those produced in Waldenstrom's macroglobulinemia or multiple myeloma, sometimes behave like cryoglobulins, the mixed IgM-IgG immune complexes produced in some chronic infectious diseases, most commonly hepatitis C. Cryoglobulinemia can cause inflammation of small vessels, resulting in purpura. The presence of cryoglobulins can be detected by laboratory tests.

Hypergammaglobulinemic purpura is a vascular purpura and is detected predominantly in women. Recurrent, small, palpable, hemorrhagic skin lesions are localized on the lower extremities. These lesions leave small residual brown spots. Many patients have manifestations of other immunological diseases (e.g., Sjogren's syndrome, SLE). The diagnostic finding is a polyclonal increase in IgG (diffuse hypergammaglobulinemia in serum protein electrophoresis).

Hyperviscosity syndrome results from markedly elevated plasma IgM concentrations and may cause purpura and other forms of pathological bleeding (eg, profuse epistaxis) in patients with Waldenstrom's macroglobulinemia.

[ 7 ], [ 8 ], [ 9 ]