Causes and pathogenesis of nosebleeds

Depending on the causes of occurrence, nosebleeds are divided into post-traumatic (including surgical trauma) and spontaneous. Spontaneous nosebleeds are a symptom of various pathological conditions and diseases, which can be both local and general in nature.

Etiological factors of a general nature leading to the occurrence of nosebleeds can be divided into four groups, taking into account possible disturbances of three interacting functionally structural components of hemostasis: vascular, platelet and coagulation.

• Changes in the vascular wall of the mucous membrane of the nasal cavity (impaired vascular hemostasis):
  • dystrophic processes in the mucous membrane of the nasal cavity (atrophic rhinitis, dry anterior rhinitis, curvature of the nasal septum, ozena, perforation of the nasal septum);
  • chronic specific inflammation (tuberculosis, syphilis);
  • tumors of the nose and paranasal sinuses (benign: angiomatous polyp, capillary hemangioma, cavernous; malignant: cancer, sarcoma; borderline: angiofibroma of the nasopharynx, inverted papilloma of the nose)
  • anomalies in the development of the vascular wall (microangiomatosis, varicose veins, hereditary hemorrhagic telangiectasia):
  • Wegener's granulomatosis,
• Violation of coagulation hemostasis:
  • hereditary coagulopathies (hemophilia, von Willebrand disease, deficiency of factors IIV, VII, X, XIII, a/hypo- and dysfibrinogenemia; protein Z deficiency);
  • acquired coagulopathies (deficiency of vitamin K-dependent blood coagulation factors due to autoimmune myeloproliferative diseases, liver pathology, incorrect therapy with acenocoumarol, acetylsalicylic acid, non-steroidal anti-inflammatory drugs, sulfonamides, antibiotics, barbiturates, etc.; DIC syndrome; acquired von Willebrand syndrome against the background of systemic lupus erythematosus, scleroderma, myelo- and lymphoproliferative diseases, dysglobulinemia, solid tumors; acquired deficiencies of plasma factors that determine the intrinsic pathway of blood coagulation, against the background of infectious and autoimmune diseases; overdose of direct and indirect anticoagulants; overdose of protamine sulfate, etc.).
• Violation of platelet hemostasis:
  • thrombocytopathy (congenital, hereditary and acquired);
  • thrombocytopenia (congenital, hereditary and acquired).
• Combined violation of various links of hemostasis:
  • diseases accompanied by increased blood pressure and damage to the vascular endothelium (hypertension, transient and symptomatic hypertension, atherosclerosis);
  • liver diseases (toxic, infectious, parasitic, autoimmune, cirrhosis) and mechanical jaundice;
  • kidney diseases (acute nephritis, exacerbation of chronic glomerulonephritis, uremia);
  • blood diseases (acute and chronic hemoblastoses, polycythemia, etc.)
  • infectious diseases (measles, scarlet fever, malaria, rickettsiosis, adenovirus infection, etc.).

Among the local causes of nosebleeds, vascular tumors play an important role. Hemangiomas (capillary and cavernous) are observed in the nasal cavity on the septum (mainly in the cartilaginous section), in the lower and middle conchae, and much less frequently in the area of the choanae and paranasal sinuses. Most hemangiomas are considered a "bleeding polyp" of the nasal septum.

Hereditary hemorrhagic telangiectasia (Rendu-Osler disease) is one of the causes of recurrent nosebleeds, which are a kind of marker of this disease. They most often begin before the age of 20, occur without apparent cause or when blowing the nose.

The morphological substrate of the disease is dysplasia of the vascular wall with a sharp thinning or absence of the muscle layer and elastic fibers.

With age, mesenchymal dysplasia increases, which contributes to the progressive development of vascular ectasia. Such morphological changes disrupt the contractility of the vascular wall and lead to the occurrence of spontaneous recurrent bleeding of the angiomatous type.

Telangiectasias on the skin and mucous membranes are one of the most striking symptoms of Rendu-Osler disease. Macroscopically, they look like dark red spots the size of a millet grain to a pea, slightly protruding above the surface, dense to the touch. Telangiectasias are localized on the arms and hands (on the palms, in the area of the nail phalanges), on the mucous membrane of the nasal cavity, tongue, lips.

Quite typical is the absence of changes in the blood coagulation system, although in a number of patients local fibrinolysis in the telangiectasia zone and signs of chronic hypochromic anemia can be detected.

Diseases characterized by hereditary, congenital or acquired disorders of hemostasis of a systemic nature constitute a group of hemorrhagic diathesis.

Among hereditary coagulopathies, 83-90% of cases are due to various types of deficiency of factor VIII (hemophilia A - 68-78%, von Willebrand disease - 9-18%) and 6-13% of cases are due to deficiency of factor IX (hemophilia B). Thus, deficiency of two coagulation factors (VIII and IX) accounts for 94-96% of all hereditary coagulopathies. Deficiency of other factors (XI, II, VII, X), hypo- and afibrinogenemia account for only 4-6% of observations, so they are combined into the subgroup "other".

In the group of acquired coagulopathies, secondary forms prevail, differing from hereditary ones by a more complex pathogenesis. A number of diseases and syndromes are characterized by the development of two, three or more independent or pathogenetically related hemostasis disorders. Such polysyndromic disorders are inherent in liver, kidney diseases, and leukemia. We have identified these diseases as a separate subgroup of combined hemostasis disorders. At the same time, in some coagulopathies, hemorrhagic manifestations are caused by very specific mechanisms. For example, nosebleeds in enteropathy and intestinal dysbacteriosis of drug genesis are caused by insufficient formation of vitamin K in the intestine, which entails a violation of the synthesis of VII, X, II, IX coagulation factors. Similar disorders are observed with competitive displacement of vitamin K from metabolism by its functional antagonists - acenocoumarol, phenindione and other indirect anticoagulants,

Complex deficiency of K-vitamin-dependent coagulation factors occurs in two more pathogenetic variants: with mechanical jaundice (impaired absorption of fat-soluble vitamin K due to the absence of bile in the intestine) and with damage to the liver parenchyma (impaired synthesis of VII, X, II and IX factors in hepatocytes). However, in these forms, other mechanisms are also involved in the development of nosebleeds (DIC syndrome, impaired factors V, IX, I and fibrinolysis inhibitors, the appearance of pathological proteins), so they belong to the subgroup of combined hemostasis disorders.

DIC syndrome is one of the most frequent and severe forms of hemostasis pathology. According to the summary statistics of large multidisciplinary clinical centers, generalized infections (bacterial and viral), including septicemia, occurring as acute septic shock, rank first among the causes of DIC syndrome. In addition to sepsis, DIC syndrome, which has many triggers, can complicate the course of acute renal failure, acute intravascular hemolysis, malignant tumors (most often lung and prostate cancer), pathology of pregnancy and childbirth, and other pathological conditions and diseases.

In the classification of causes of nosebleeds there are four subgroups of drug-induced hemostasis disorders. Some authors do not consider it possible to combine them, since the pathogenesis of coagulopathies caused by different drugs has fundamental differences. Thus, an overdose of an anticoagulant of spicy action (sodium heparin) blocks almost all coagulation factors belonging to serine proteins (XIIa, XIa, IXa, Ha): drugs with hapten properties (quinidines, sulfonamides, aminosalicylic acid, digitoxin, rifampicin, hydrochlorothiazide, gold preparations, etc.) cause immune thrombocytopenia: salicylates, pyrazolone derivatives and similar drugs induce the development of thrombocytopathy; Indirect anticoagulants competitively displace vitamin K from metabolism. It is impossible to ignore the significant differences in the pathogenesis of drug-induced coagulopathies, since this is determined by the need for differentiated pathogenetic treatment.

In the group of platelet hemostasis disorders, thrombocytopathy is of particular interest, in which nosebleeds are the dominant type of bleeding, and in some cases, the only symptom of the disease. In the latter case, diagnosis of the disease is especially difficult due to the lack of changes in traditional blood tests and coagulogram, and most nosebleeds of unclear etiology are actually a manifestation of thrombocytopathy.

Thrombocytopathies are divided into congenital, hereditary and acquired. Hereditary forms are grouped by types of dysfunction, morphological and biochemical disorders of platelets. Acquired thrombocytopathies are observed in hypothyroidism, developing both spontaneously and after strumectomy, with hypoestrogenism. Secondary thrombocytopathies can be caused by hemoblastoses, myeloproliferative diseases, vitamin B12 deficiency, progressive renal or hepatic insufficiency, paraproteinemic hemoblastoses, massive blood transfusions, DIC syndrome. In these cases, a decrease is observed primarily in the aggregation function of platelets, which in some patients is manifested by petechial hemorrhages on the skin and mucous membranes, nose and gum bleeding,

Most acquired forms of platelet pathology are characterized by the complexity of genesis, heterogeneity of functional disorders, combination with other hemostasis disorders, in connection with which they are included in the group of combined disorders. Thus, the "background" hemostasis disorder in acute leukemia is hyporegenerative thrombocytopenia, combined with qualitative inferiority of platelets, but at any stage of the development of these diseases, DIC syndrome may join in,

Nosebleeds in uremia are caused by qualitative inferiority of platelets, thrombocytopenia and dystrophic changes in the mucous membrane of the nasal cavity, which occur as a result of the release of nitrogenous metabolism products. In nephritic syndrome, nosebleeds are caused by DIC syndrome, deficiency of IX, VII or II coagulation factors, caused by their greater loss with urine, as well as renal arterial hypertension, which entails endothelial dysfunction and increased "fragility" of small vessels.

Determining the cause of nosebleeds creates the basis for forming a detailed diagnosis, which determines a differentiated approach to the treatment of this pathology.

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Pathogenesis of nosebleeds

The most common cause of nosebleeds is arterial hypertension. Although nosebleeds in this group of patients are observed mainly during periods of increased blood pressure, their immediate cause is not a mechanical rupture of blood vessels, but disturbances in microcirculation and coagulation properties of the blood, leading to the development of localized intravascular coagulation. Chronic subcompensated DIC syndrome and endothelial dysfunction are an integral part of the pathogenesis of arterial hypertension. Until a certain time, the system of regulation of the aggregate state of blood in this group of patients is in a state of fragile equilibrium, which can be disturbed by a minimal stimulus (blood loss, medical manipulation, stress, physical activity, intake of certain medications). If one or more local "permitting" factors are present (damage to the endothelium, dilation of pathologically altered vessels, slowing of blood flow or stasis in the microcirculatory bed, opening of arteriovenous shunts, increased blood viscosity), localized intravascular blood coagulation develops with necrosis of the vascular wall and hemorrhagic syndrome, manifested by hemorrhagic stroke, hemorrhagic myocardial infarction or nosebleed.

In thrombocytopenia and thrombocytopathy, the occurrence of nosebleeds is due to disturbances in vascular-platelet hemostasis. The angiotrophic function of platelets ensures normal permeability and resistance of the walls of microvessels. Platelet deficiency leads to endothelial dystrophy, disturbance of its athrombogenicity, increased permeability of the vascular wall for plasma and erythrocytes, which is manifested by petechiae. With severe thrombocytopenia, hemorrhagic syndrome develops. Bleeding with disturbances in vascular-platelet hemostasis tends to recur, since the quantitative and qualitative deficiency of platelets disrupts both primary hemostasis (disruption of platelet adhesion and aggregation, delivery of plasma coagulation factors and biologically active substances to the bleeding site) and retraction of the blood clot, necessary for the formation of a full-fledged thrombus.

Thus, in the pathogenesis of spontaneous nosebleeds, an important place is occupied by systemic disorders of coagulation and platelet hemostasis, disruption of microcirculation in the mucous membrane of the nasal cavity, changes in the athrombogenicity of the endothelium, a decrease in the contractile properties of blood vessels, and an increase in vascular permeability.