OVERVIEW
Bleeding disorders are a collective term for a group of disorders caused by abnormalities in the hemostatic mechanism. Hemorrhagic diseases can be divided into two categories: hereditary and acquired, and their clinical manifestations are mainly bleeding from different parts of the body. There are many types of hemorrhagic diseases with different pathogenic mechanisms, and clinical treatment should be given according to different causes and pathogenic mechanisms.
Causes
1. Abnormalities of blood vessel wall
(1) Congenital or hereditary
Such as hereditary capillary dilatation, familial purpura, giant cavernous hemangioma, generalized diffuse angiokeratosis, ataxia capillary dilatation.
(2) Acquired
1) Immune such as anaphylactic purpura, drug-allergic purpura, autoimmune purpura and so on.
2) Non-immune such as vitamin C deficiency, mechanical purpura, purpura simplex, infectious purpura, corticosteroid purpura, senile purpura and purpura corporis.
2. Platelet abnormalities
(1) Abnormal platelet count
(1) Reduced platelet production Hereditary: e.g. Wiskott-Aldrich syndrome, Trousseau syndrome, Mediterranean thrombocytopaenia with giant platelets, Alport syndrome, Chediak-Higashi syndrome, Fanconi anemia, thrombocytopaenia with radial deficiency syndrome, etc.
Acquired: such as aplastic anemia, neoplastic bone marrow infiltration such as leukemia, etc., inhibition of megakaryocyte and platelet production due to physicochemical and biological factors (e.g., radiation, drug, infection, etc.).
(2) excessive platelet consumption or destruction ① immune such as immune thrombocytopenic purpura, drug-induced immune thrombocytopenic purpura, connective tissue disease (such as systemic lupus erythematosus, etc.). ② non-immune such as diffuse intravascular coagulation, thrombotic thrombocytopenic purpura, heparin thrombocytopenia, drug-induced non-immune thrombocytopenic purpura.
3）Thrombocytosis
Such as primary thrombocytosis and other myeloproliferative disorders some patients may have bleeding manifestations.
(2) Abnormal platelet quality
(1) Hereditary, such as platelet apathy, Bernard-Soulier syndrome.
(2) Acquired: Bleeding symptoms may be caused by abnormal platelet quality due to antiplatelet drugs, infections, uremia, dysglobulinemia, liver disease, and myeloproliferative disorders.
3. Abnormal quantity and quality of coagulation factors
It can also be divided into two categories: hereditary and acquired.
(1) Hereditary, such as hemophilia A, B and hereditary Ⅱ, Ⅴ, Ⅶ, X, Ⅺ, Ⅻ, Ⅷ factor and fibrinogen deficiency.
(2) Acquired, such as vitamin K-dependent coagulation factor deficiency, coagulation factor abnormality caused by liver disease, and acquired coagulation factor inhibitors.
4. Anticoagulation and fibrinolytic abnormality
Such as overdose of anticoagulant or thrombolytic drugs, snakebite, rat poison, etc.
Symptoms
The clinical manifestations of bleeding disorders are mainly bleeding from different sites. For the initial evaluation of bleeding disorders, detailed questioning of the patient’s bleeding history, family history, symptoms and careful examination of the patient’s bleeding signs are very important for the patient’s diagnosis. In taking the history, attention should be paid to the patient’s gender, age at the time of bleeding, bleeding frequency, medication, surgery, history of trauma, and the absence of a family history, etc. The clinical manifestations are often due to the pathogenesis of the bleeding.
Clinical manifestations often vary depending on the pathogenesis.
1. Bleeding under the skin and mucous membrane
Various bleeding disorders, especially vascular and platelet disorders, the most common and easily found signs and symptoms are skin and submucosal bleeding. The following types of hemorrhage can be seen depending on the degree and extent of bleeding and the location of the bleeding.
(1) Hemorrhagic spot refers to bleeding on the skin with a diameter of 2mm or less, mostly the size of a pinhead, usually not higher than the skin surface, and does not lose color when pressed. It is dark red in the early stage and is completely absorbed within 1 to 2 weeks. Bleeding spots can be scattered throughout the body, more common in the limbs, the lower part of the trunk is more common.
(2) Purpura is subcutaneous hemorrhage with a diameter of 3~5mm, which is not higher than the skin surface and does not fade away with suppression; its nature, characteristics, location and clinical significance are the same as that of hemorrhagic spots.
(3) Bruises are subcutaneous flaky hemorrhages more than 5 mm in diameter, with the same distribution as hemorrhagic spots and purpura. Single and multiple small flaky bruises, generally suggesting vascular or platelet disease; large bruises are common in severe thrombocytopenia or functional defects and severe coagulation dysfunction.
(4) Blood blisters Blood blisters on oral mucosa are often the manifestation of severe thrombocytopenia.
(5) Nosebleed Platelet disorders and hereditary capillary dilatation are common. However, under the condition of high temperature and dry climate, nosebleed can also occur in normal people. If only one side of the nose bleeds, local vascular factors are more likely than coagulation dysfunction.
(6) Gum bleeding is a common symptom of platelet disorders and vascular diseases.
2. Deep tissue bleeding
Deep tissue hemorrhage is common in deeper subcutaneous, muscular, joint and plasma cavities.
(1) Hematoma Deeper subcutaneous, muscle and other soft tissue bleeding. When the hematoma is large, it may cause distension, pain and dysfunction due to compression of neighboring tissues and organs. Mild trauma or spontaneous hematoma is common in coagulation mechanism disorder, such as hemophilia.
(2) Joint bleeding is common in weight-bearing joints such as knee, ankle, elbow, wrist and hip joints. Early joint swelling and pain can be seen, and joint puncture can draw out old blood that is not easy to be coagulated. Repeated joint bleeding can lead to permanent deformity and severe functional impairment. Joint hemorrhage is commonly caused by coagulation mechanism disorder, such as hemophilia.
(3) Plasma membrane cavity bleeding is mainly seen in abdominal cavity, pleura, pericardium and testicular sheath bleeding. Unexplained or spontaneous plasma cavity hemorrhage is often seen in coagulation mechanism disorders, such as hemophilia.
(4) Bleeding from the fundus of the eye is mostly seen in severe thrombocytopenia and severe vascular lesions, while other bleeding disorders are less common.
3. Visceral hemorrhage
Visceral hemorrhage can be clinically manifested as hemoptysis, vomiting blood, hematochezia, hematuria, hemoptysis and central nervous system hemorrhage, and the amount of bleeding is large. In addition to the symptoms of the corresponding organs and systems, it can also be accompanied by circulatory disorders caused by blood loss, and even shock and other symptoms. It is mainly seen in severe thrombocytopenia and coagulation factor deficiency.
Examination
According to the patient’s history and physical examination, to determine whether there is hemostatic dysfunction and analyze the possible etiology, laboratory examination is crucial to the diagnosis of bleeding disorders.
1. Screening tests
Including capillary fragility test, platelet count, priming time, clotting time, partially activated prothrombin time, prothrombinogen time, prothrombin time, and so on.
2. Confirmatory tests
(1) Vascular abnormality Including capillaroscopy and vWF measurement.
(2) Platelet abnormality: platelet adhesion and aggregation test.
(3) Coagulation abnormality, including determination of antigen and activity of various coagulation factors, thrombin generation and correction test.
(4) Anticoagulant abnormality Including antithrombin III antigen and activity or thrombin-antithrombin complex, protein C, lupus anticoagulant assay.
(5) Abnormalities of fibrinolysis, including ichthyosin paracoagulation test, fibrinogen degradation products, D-dimer, fibrinogen assay, and so on.
3. Special examination
For some hereditary diseases and some rare hemorrhagic diseases, some special tests such as protein structure analysis, gene determination and immunopathological examination are needed to confirm the diagnosis.
Diagnosis
1. Medical history
It is important to know the bleeding history of the patient, and the following aspects should be noted:
(1) Bleeding type Petechiae and ecchymoses on the skin and mucous membranes are usually suggestive of platelet or vascular hemorrhage, while elevated petechiae are usually suggestive of vascular hemorrhage. If deep tissue (muscle and joint cavity) bleeding is dominant, it suggests coagulation factor deficiency. In addition, the former two often in the trauma can be immediate bleeding, short duration; the latter occurs slowly, long duration.
(2 Bleeding triggers A history of drug exposure is mostly suggestive of platelet sex; if bleeding does not stop after minor injuries, it is mostly coagulation factor disorder.
(3) Family history Because hereditary bleeding disorders often have a certain hereditary pattern, grandparents, parents and siblings, as well as maternal grandparents and uncles should be asked whether there is a history of similar diseases and bleeding history.
2. Physical examination
Observe the pattern and distribution of bleeding, whether it is symmetrical, flat or above the skin surface. There is no muscle bleeding or joint cavity bleeding, and there is no systemic disease manifestation.
3. Laboratory examination
According to the history and physical examination may provide some diagnostic clues, first use some simple laboratory tests for screening, to identify at that point, and then do more complex confirmatory tests.
Questions you may be concerned about
What are the classifications and etiologic diagnoses of bleeding disorders?
The main classifications of bleeding disorders are abnormal bleeding of the vessel wall, abnormal bleeding of platelets, abnormal bleeding of coagulation, abnormal bleeding of anticoagulation and fibrinolysis, and abnormal bleeding of complex hemostatic mechanisms.
1. Vascular wall anomalous hemorrhage includes etiology: familial simple allergic purpura, sepsis, and so on.
2. Platelet anomalous hemorrhage including etiology: thrombocytopenia such as aplastic anemia, excessive platelet destruction such as idiopathic thrombocytopenic purpura, excessive platelet consumption such as disseminated intravascular coagulation, and platelet quality abnormalities such as platelet apoplexy.
3. Coagulation abnormal bleeding including etiology: hemophilia, hereditary fibrinogen deficiency and reduction, vitamin K deficiency.
4. Complex hemostatic mechanism abnormal bleeding including etiological diagnosis: vascular hemophilia, disseminated intravascular coagulation.
There are many causes of bleeding disorders, and when such disorders occur, the causes should be clarified in time and targeted treatment should be taken.
Treatment
There are many kinds of hemorrhagic diseases with different pathogenesis, and corresponding treatment measures should be given according to different causes and pathogenesis.
1. Treatment of hemorrhagic diseases caused by vascular factors
In addition to the treatment of etiology, bleeding caused by simple vascular factors is generally treated with drugs that reduce the fragility and permeability of blood vessels (such as Lutin, sodium carolinium, phenol sulfonyl ethylamine, vitamin C, blood coagulation tablets, adrenocorticotropic hormone, and vasoconstrictors (such as posterior pituitary hormone, ephedrine and so on) can be selected according to the amount of savings in the treatment.
2. Treatment of hemorrhagic diseases caused by platelet factors
(1) Drugs to promote platelet generation
(1) Thrombopoietin (TPO) TPO is involved in the whole process of megakaryocyte proliferation, differentiation, maturation and division to form functional platelets.
(2) IL-11 Acts on primitive hematopoietic stem cells in bone marrow cells, causing an increase in megakaryotic lineage progenitor ploidy, promoting megakaryocyte maturation, and increasing the number of peripheral platelets.
(2) Platelet-enhancing drugs Bactrim may promote platelet activation and induce platelet aggregation.
(3) Adrenocorticotropic hormone Mainly through the inhibition of platelet antibody production, blocking macrophage Fc receptors, so that platelets attached with antibodies or immune complexes in the mononuclear phagocyte system to reduce the destruction, so that platelets in the spleen to reduce the retention of platelets, improve the number of peripheral platelets. It is mainly used to treat immune thrombocytopenic purpura. Generally use prednisone.
(4) Immunosuppressants Immunosuppressants such as vincristine, cyclophosphamide, azathioprine, cyclosporine, etc. can reduce the production of platelet antibodies by suppressing immunity.
(5) Splenectomy Ineffective drug treatment or obvious reduction of platelets due to hypersplenism, splenectomy can be considered to reduce the site of platelet destruction.
(6) Platelet transfusion In principle, it should only be used for serious bleeding caused by abnormal quantity or quality of platelets due to various reasons. When the platelet count is less than 20×109/L, it is often accompanied by extensive and serious bleeding, such as hemoptysis, gastrointestinal bleeding, intracranial hemorrhage and so on. Prophylactic and therapeutic platelet transfusion is the most effective treatment. When the platelet count is more than 20×109/L, the bleeding is usually mild, and platelet transfusion is usually not necessary, so as to avoid the production of homologous antiplatelet antibodies after repeated platelet transfusion, which will reduce the efficacy of platelet transfusion in the future when it is needed urgently.
3. Treatment of bleeding disorders caused by coagulation disorders
Depending on the pathogenesis, coagulation factor deficiency diseases can be treated with vitamin K supplementation (prothrombin, FⅦ, FⅨ, FⅩ deficiency) and plasma and blood product supplementation (congenital coagulation factor deficiency).