Coagulopathy are hematological syndromes characterized by a violation of hemostasis by the type of hypo- or hypercoagulation. Hemocoagulation disorders are manifested by hemorrhagic syndrome (nosebleeds, gums, wounds, subcutaneous hemorrhages), thrombosis of various localization. Pathology are diagnosed according to hematological studies: UAC, coagulogram, coagulation factors, platelets, autoantibodies, etc. Therapy depends on the impaired link of hemostasis, may include blood transfusions, the appointment of glucocorticoids, vitamins, anticoagulants, surgical intervention.
Coagulopathy combine various conditions accompanied by both a decrease and an increase in blood clotting. According to WHO statistics, about 5 million people in the world suffer from hemorrhagic syndrome. Hemostasis disorders are detected in the laboratory in 66%, and clinically in 16% of ICU patients. Not only specialists in the field of hematology, but also obstetricians-gynecologists, pediatricians, surgeons, traumatologists, cardiologists can face hemocoagulation disorders in everyday practice. Coagulopathy significantly aggravate the prognosis of major diseases, require urgent medical care.
The main mechanism of hemostasis disorders is an imbalance in the coagulation and anticoagulation systems of the blood. Coagulopathy develop under the influence of hereditary, endogenous and exogenous factors. The main groups of reasons:
- Genetic background. Hereditary hemostasis pathologies are associated with molecular defects of plasma and platelet coagulation factors, congenital anomalies of the vascular wall. Deficiency of factors VIII and IX is the basis of hemophilia, Willebrand factor deficiency is the basis of Willebrand disease, factor VII is hypoproconvertinemia, factor X is Stewart‒Prauer disease, etc. An example of thrombocytopathies is Glanzman’s thrombasthenia.
- Concomitant conditions. Hypocalcemia, hypovitaminosis K, hemodilution, bleeding have an effect on the function of hemostasis. Coagulopathy are accompanied by bacterial (sepsis) and viral infections (haemorrhagic fevers, COVID-19), oncopathologies (acute leukemia), liver diseases (cirrhosis, Budd–Chiari syndrome), snake bites of the viper family.
- Pharmacotherapy. Incorrect selection of the dosage of antiplatelet agents and anticoagulants leads to thrombocytopathies and hypocoagulation. Hypercoagulation is a side effect of COCs, corticosteroids. The use of large volumes of colloidal solutions to replenish BCC can cause hemorrhagic syndrome.
- Autoimmune reactions. Autoimmune coagulopathy caused by the formation of antibodies to clotting factors are isolated in a separate group. The triggers are transmitted infections, vaccination, insolation, radiation. The most frequent and clinically significant in this regard are antiphospholipid syndrome, idiopathic thrombocytopenic purpura, HELLP syndrome, etc.
- Medical manipulations. The risk of hypercoagulation exists when blood comes into contact with artificial materials (valve prostheses, intravascular stents, IC devices, ECMO, etc.).
The main structural and functional components of hemostasis are the vascular wall, shaped elements of blood and plasma coagulation factors. Primary (vascular-platelet) hemostasis is carried out by the vascular endothelium and subendothelium together with platelets. Secondary (coagulation) hemostasis is realized by plasma coagulation and anticoagulation factors. Coagulopathy can develop with the pathology of any of these links.
A normal intact vascular wall has antithrombotic properties, which ensures unhindered blood circulation through the vessels. Various pathogenic factors (bacterial toxins, CEC, proinflammatory cytokines) cause damage to the endothelium, as a result of which its procoagulant properties are enhanced.
There is increased adhesion and aggregation of platelets, activation of plasma factors with simultaneous inhibition of anticoagulant factors and fibrinolysis. Hypercoagulation leads to the formation of intravascular thrombi, tissue ischemia and organ infarctions. With DIC syndrome, generalized thrombosis and multiple organ failure develop.
Coagulopathy occurring by the type of hypocoagulation can be caused by vascular diseases (vasopathies), a decrease in the number of platelets (thrombocytopenia) or their defects (thrombocytopathy), a deficiency of clotting factors, increased anticoagulant or fibrinolytic activity (hemostasiopathy). At the same time, increased bleeding develops ‒ hemorrhagic syndrome.
According to the time and causes of occurrence, coagulopathic syndromes are divided into hereditary and acquired. According to the nature of changes in hemostasis, hypocoagulation and hypercoagulation are differentiated. Taking into account the clinical manifestations , the following types of coagulopathy are distinguished:
- Thrombophilic – characterized by the occurrence of thrombosis and thromboembolism (AFS, polycythemia, hemorrhagic vasculitis).
- Hemorrhagic – manifested by a tendency to spontaneous and post-traumatic bleeding (hemophilia, afibrinogenemia, Glanzman’s thrombasthenia, hemorrhagic disease of newborns, etc.).
- Thrombohemorrhagic – occur with multiple thrombosis and hemorrhages (DIC syndrome).
Depending on the impaired link of the coagulation system, three classes of acquired coagulopathy are distinguished:
- Pathologies of platelet hemostasis: Moshkovitsa disease, Werlhof disease, HELLP syndrome, thrombocytopathies.
- Pathologies of coagulation hemostasis: overdose of anticoagulants, hemophilia, vitamin K deficiency.
- Mixed hemostasis disorders: liver diseases, uremia, multiple organ dysfunction.
There is also a division of coagulopathy into the following groups:
- vasopathy – vascular wall lesion (Randu-Osler disease, Kazabach-Merritt syndrome, capillarotoxicosis);
- thrombocytopathies – structural and functional abnormalities of platelets (Glanzmann’s thrombasthenia, Willebrand’s disease);
- thrombocytopenia – quantitative reduction of platelets (Werlhof’s disease);
- hemostasiopathies – deficiency of clotting factors, increased fibrinolysis (K-dependent coagulopathy, liver pathology).
Hypercoagulation syndromes are characterized by a high risk of thrombosis. Clinical manifestations may be completely absent, then coagulopathy is diagnosed only in the laboratory. In other cases, there is rapid blood clotting with small wounds, thrombosis of venous catheters and needles during blood collection.
The clinic of symptomatic thrombosis depends on the type and caliber of the clogged vessel, the localization of the blood clot. Serious danger is represented by infarctions of organs: heart, brain, kidneys, intestines, lungs. Arterial thrombosis leads to myocardial infarction, ischemic stroke, occlusion of mesenteric vessels, gangrene of extremities, fetal loss in pregnant women. Deep vein thrombosis is a source of pulmonary embolism.
The most typical clinical sign of thrombosis is pain depending on the location of the thrombus: headache in the chest, abdomen, lower back, etc. Weakness, shortness of breath, numbness of limbs, convulsions are possible. Without timely medical care, irreversible necrosis of the organ occurs, often fatal.
Hemorrhagic syndromes are accompanied by increased bleeding. Bleeding of the capillary type is manifested by the formation of petechiae and ecchymoses on the skin, nasal bleeding, menorrhagia, and sometimes intracerebral hemorrhages.
Hematomic bleeding leads to hemorrhages in the body cavity and muscles. With coagulopathy of this kind, painful subcutaneous hematomas, hemarthrosis, retroperitoneal hematomas are formed. Gastrointestinal bleeding, hematuria, prolonged bleeding after wounds, tooth extraction, surgical operations may occur.
Angiomatous bleeding develops from abnormal vessels: angiomas, telangiectasias, arteriovenous malformations. Vasculitis-purple bleeding is characterized by the presence of hemorrhagic rash, inflammatory erythema, nephritis against the background of systemic vasculitis.
The consequence of hemorrhagic coagulopathy is iron deficiency anemia. Simultaneous massive blood loss can lead to hemorrhagic shock and death.
Hematologists-hemostasiologists, cardiologists, immunologists, phlebologists, etc. take part in the diagnosis of coagulopathy. The main diagnostic criteria are laboratory indicators of various links of hemostasis:
- Coagulological test. The extended coagulogram includes about 20 different positions: prothrombin and thrombin time, INR, PTI, bleeding time, APTT, ethanol test, Willebrand factor, antithrombin III, fibrinogen, D-dimer, plasminogen, etc. The number and morphology of platelets are investigated. If necessary, thromboelastography is performed.
- Serological test. If AFS is suspected, antibodies to beta-2-glycoprotein, cardiolipin, ANF, lupus anticoagulant are searched. With thrombocytopenic purpura, At to platelets are examined, with vasculitis ‒ At to the cytoplasm of neutrophils.
- Other hematological test. Clinical urine and blood tests, biochemical studies (calcium, vitamin K, liver enzymes, etc.) are mandatory. For various coagulopathy, a syndromic gene diagnosis, a bone marrow biopsy with a myelogram study may be required.
- Instrumental research. Diagnosis of thrombosis is carried out using ultrasound (ultrasound of arteries and veins) and X-ray (angiography) methods. In case of bleeding, endoscopic examinations (gastroscopy, colonoscopy, bronchoscopy, laparoscopy), echography (ultrasound of the retroperitoneal space, joints, soft tissues) are resorted to.
Antiplatelet agents, anticoagulants of indirect and direct action, fibrinolytic drugs, angioprotectors are used in the treatment of thrombosis. With venous thrombosis, ischemic stroke, regional catheter thrombolysis is resorted to. In order to remove CEC, toxins, fibrinolysis products from the bloodstream, plasmapheresis, cytapheresis is performed. In autoimmune coagulopathy, glucocorticosteroids, cytostatics, and immunoglobulins are prescribed.
For the relief of coagulopathy accompanied by bleeding, local and general hemostasis is carried out. In all cases, except for symptomatic treatment, etiopathogenetic therapy is necessary.
- Local hemostasis. Hemostatic sponges, fibrin glue, electrocoagulation are used to stop capillary bleeding. Injection hemostasis, sclerotherapy, irrigation with hemostatic solutions are widely used.
- Systemic hemostatic therapy. Injections of coagulants, vitamin K, calcium chloride infusion, antifibrinolytics are used to stop bleeding. Blood transfusions may consist in transfusion of freshly frozen plasma, platelet mass, thromboconcentrate, cryoprecipitate.
- Surgical hemostasis. In the absence of the effect of conservative therapy, various methods of minimally invasive (balloon tamponade, endoscopic vascular clipping) or radical surgical hemostasis (splenectomy, hysterectomy, etc.) are resorted to.
Prognosis and prevention
Any hemostatic disorders are potentially life-threatening. However, if all precautions are taken and medical recommendations are followed, the risk of fatal bleeding and thrombosis is minimal. To prevent acquired coagulopathy, one should not start chronic diseases, take medications uncontrollably, be exposed to excessive insolation and other adverse exogenous influences. Prevention of hereditary coagulopathy is possible only through genetic screening.
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