STUDY - Technical - New Dacian's Medicine
Hemorrhage
and Thrombosis (2)
Translation Draft
And this is going to be a slightly longer post because I want to finish this "group"...
I'll continue with the clinical evaluation, based on the history. Some elements of anamnesis are useful to determine whether a hemorrhage is caused by a disturbance of hemostasis or a local anatomical defect. A first element would be a history of hemorrhage after ordinary local trauma, such as a dental extraction, birth or minor surgery.
Hemorrhage large enough to require a transfusion requires special attention. A family history of bleeding or bleeding with multiple sites that cannot be explained by trauma or surgery also suggests a systemic condition. Since bleeding may be moderate, the absence of a family history does not exclude an inherited hemostasis condition. The defect can be located in platelets or plasma clotting system.
Hemorrhage due to platelet defects is usually superficial, localized in the skin and mucous membranes, occurs immediately after trauma or surgery and is easily controllable by local treatment. Hemorrhages that occur as a result of a defect in secondary hemostasis (plasma coagulation system) occur within hours or days of the injury and are not influenced by local therapy. This type of hemorrhage is most commonly located in the body's subcutaneous tissue, muscles, joints and cavities. A careful and meticulous history is probably the most important step in establishing the presence of a hemostasis disorder and guiding initial laboratory tests.
Associated with a careful history, the physical examination provides useful information for the evaluation of patients with hemostasis disorders. The most common location where hemorrhages can be observed is the skin and mucous membranes. Blood collections in the skin are called purple and can be classified according to the location of the haemorrhage. Small, punctual, intradermal haemorrhages, due to the extravasation of hematoids from the capillaries, are called spots and are characteristic for platelet defects, especially for severe thrombocytopenia.
Larger subcutaneous collections, due to the extravasation of blood from arterioles and small venus, represent bruising (bruising) or, if deeper and palpable, hematomas. They are common in patients with platelet defects and follow after minor trauma. There are other skin and mucous lesions, such as capillary dilation, telangiectasis, which can cause bleeding in the absence of any hemostasis disorders. In addition, the loss of connective tissue support for capillaries and small veins, which occurs with age, increases the fragility of superficial veins, such as those on the dorsal face of the hand, leading to the extravasation of blood in the subcutaneous cell tissue, senile purpura.
Menorrhagia is often a serious problem for women with severe thrombocytopenia or platelet dysfunction. In addition, patients with primary hemostasis disorders, especially those with von Willebrand disease, may have recurrent gastrointestinal bleeding. As mentioned above, bleeding in the serous, retroperitoneal or joint cavities is a frequent manifestation of plasma clotting deficits. Repeated joint bleeding can lead to thickening of the synovial, chronic inflammation, the appearance of fluid collections and can erode the articular cartilage, causing chronic joint deformities, with limitation of mobility.
Such deformities are present especially in patients with factor VIII and IX deficiency, the two sex-linked coagulation disorders, called hemophilias. For unclear reasons, hemarthrosis is uncommon in other defects of plasma coagulation. Blood collections in the serous cavities or soft tissues can cause secondary tissue necrosis or nerve compression. Retroperitoneal hematomas can produce compression of the femoral nerve, and collections of poorly coagulated blood in soft tissues can mimic a malignant transformation (pseudotumor syndrome). Hemorrhages in the oropharyngeal, where bleeding can compromise the normal functioning of the airways, and those in the central nervous system can be life-threatening. Intracerebral haemorrhages are one of the major causes of death in patients with severe clotting defects.
From the point of view of laboratory tests, the most important screening tests of primary hemostasis mechanisms are: 1. bleeding time (a sensitive indicator of platelet function) and 2. platelet count (this is very useful, being easy to achieve and correlates well with the predisposition to bleeding). Normal platelet levels are between 150,000 and 450,000 per cubic millimeter of blood. As long as the number of plaques is over 100,000 per cubic millimeter, patients remain asymptomatic and bleeding time is normal.
Patients with plaques below 50,000 per cubic millimeter experience rapid bleeding after concussions, manifested by skin purpura after minor trauma and bleeding after mucosal surgery. Patients with less than 20,000 platelets per cubic millimeter have a much increased incidence of spontaneous bleeding, usually have spots and may have intracranial or other spontaneous internal bleeding.
The main causes of thrombocytopenia are represented by: 1. decrease in medullary production of megakaryotes (a. infiltration of the marrow with tumors, fibrosis and b. medullary insufficiency in aplastic, hypoplastic or as an effect of taking drugs), 2. splenic sequestration of circulating plaques (a. hypertrophy of the spleen due to tumor infiltration and b. congestion of the spleen due to portal hypertension), 3. increased destruction of circulating plaques (a. non-immune destruction due to vascular prostheses, heart valves, disseminated intravascular coagulation, septicaemia or vasculitis and b. immune destruction due to autoantibodies to platelet antigens, antibodies associated with drug ingestion and circulating immune complexes as in the case of systemic lupus erythematosus, viral agents or bacterial septicaemia).
Patients with qualitative platelet abnormalities have a normal platelet count and a prolonged bleeding time. The disorders of primary hemostasis (of plaques) are represented by: 1. defects of platelet adhesion (with a. von Willebrand disease and b. Bernard-Soulier syndrome represented by the absence or dysfunction of glycoprotein Ib/ IX), 2. platelet aggregation defects (with Glanzmann thrombasthenia represented by the absence or dysfunction of glycoprotein IIb/ IIIa), 3. defects in platelet secretion (with a. decreased cyclooxygenase activity due to drugs such as aspirin and non-steroidal anti-inflammatory drugs or congenital cause, b. deficiencies in the deposits of granules with congenital or acquired causes and c. uremia resulting from platelet "coverages" caused, for example, by penicillin or paraprotein) and 3. platelet coagulation defects (as in the case of Scott syndrome).
The bleeding time is determined by practicing a small, superficial incision, and measuring the duration of bleeding in that area. Although it is a relatively simple "biotest", thanks to careful standardization, it has become a faithful and sensitive test of platelet function. The most widespread technique uses a type or automatic scalpel to control the length and depth of the incision (usually 1 mm deep and 9 mm long) and a sphygmanometer adjusted to 40 mmHg to evenly loosen the capillary bed in the forearm.
To be useful, bleeding time should be practiced by an experienced technician, as small differences in technique have a great effect on test results. Although any patient with a bleeding time of more than 10 minutes has a slightly increased risk of bleeding, this risk becomes significant only in patients with bleeding time values exceeding 15-20 minutes (there is an almost linear correlation between bleeding time and platelet count). When a deficiency of primary hemostasis is discovered, specialized tests are needed to determine the cause of platelet dysfunction.
An accurate diagnosis is important, as patients with bleeding due to primary hemostasis may require treatment with platelet mass, certain hormones (desmopressin, estrogens, glucocorticoids) or plasma fractions, depending on the nature of the condition. Occasionally, patients with a multiple history of bleeding, especially those with von Willebrand disease (mild form, may have a normal bleeding time on an initial test due to cyclic variations in von Willebrand factor levels). They require repeated testing to establish an accurate diagnosis.
Plasma coagulation function is easily evaluated using simple laboratory tests such as: partial thromboplastin time (TPT), prothrombin time (TP), thrombin time (TT) and quantitative determination of fibrinogen. TPT tests the intrinsic pathway of coagulation, assessing the effectiveness of factors XII, KGMM, PK, XI, IX and VIII. TP tests the extrinsic pathway, dependent on the tissue factor. Both tests assess the common coagulation pathway, involving all reactions that occur after the activation of factor X.
Prolongation of TPT and TP that is not corrected after the addition of normal plasma suggests the presence of a clotting inhibitor. When both TPT and TP are prolonged, it becomes necessary to use a specific test to assess the conversion of fibrinogen into fibrin (either TT or fibrinogen level determination can be used). When abnormalities are found in any of these tests, more specific investigations of coagulation factors may be required to determine the nature of the defect. There are a few rare coagulation abnormalities that may remain undetected because they do not alter the screening tests discussed.
These are factor XIII deficiency, plasmin alpha2 inhibitor deficiency, PAI-1 deficiency (which is the most important plasminogen activator inhibitor) and Scott syndrome, a platelet coagulation defect. A test for fibrin polymerization (dependent on factor XIII), such as clot solubility in 5-M-urea, should be requested when TP and TPT are both normal, but there is a history of frequent bleeding.
The fibrinolytic system can be investigated by measuring the lysis time of the euglobulin clot or total blood clot and for measuring the alpha2 inhibitor levels of plasmin and IAP-1. Scott syndrome can be diagnosed by measuring prothrombin time, which assesses the amount of residual prothrombin.
Diseases associated with thrombosis are: A. congenital (with 1. deficient inhibition of clotting factors: a. factor V Leiden - resistant to inhibition by activated protein C, b. antitrobin deficiency III, c. protein deficiency C, d. protein deficiency S, 2. altered clot lysis with a. disfibrinogenemia, b. plasminogen deficiency, c. tAP deficiency , d. excess PAI-1 and 3. with uncertain mechanism - as is the case with hemocystinuria) and B. acquired (with 1. diseases or syndromes with a. lupus anticoagulant, b. malignancies, c. myeloproliferative diseases, d. thrombocytopenic purpura, e. estrogenic treatment, f. hyperlipemia, g. diabetes mellitus, h. hyperviscosity, i. nephrotic syndrome, j. congestive heart failure and k. nocturnal paroxysmal hemoglobinuria and 2. , b. obesity, c. postoperative states, d. immobilization and e. old age).
There are no clinical screening tests for patients suspected of having hypercoagulability or prethrombotic disorders. In the research laboratories, tests have been developed that measure peptides of low molecular weight or complexes that inhibit enzymes generated during coagulation. For example, radioimmunological tests have been developed for fibroids A and B, thrombin-antithrombin complex and prothrombin cleavage fragments. Increased levels of these products have been reported in patients with prethrombotic or thromboembolism.
Currently, patients suspected of being hypercoagulable based on clinical data should undergo specific tests for the few defects currently known. Currently available tests can identify 10-20% of cases of familial thrombosis, which represent a small proportion of patients who report to the doctor with thromboembolic phenomena. Inhibitory syndromes or circulating anticoagulants are usually due to antibodies that decrease the activity of clotting factors. It is not a common cause of hemorrhage, and requires specific diagnostic tests.
The presence of inhibitors is likely when changes in screening tests cannot be corrected by adding normal plasma to the patient's plasma. Specific antibodies against coagulation factors may be present: 1. postpartum, 2. in patients with autoimmune diseases, such as systemic lupus erythematosus, 3. in patients using drugs such as penicillin or streptomycin and 4. in elderly patients without other diseases. In addition, of patients with severe haemophilia who have received multiple transfusions, 10 to 20% develop inhibitory antibodies.
Some patients, especially those with systemic lupus erythematosus, may have non-specific anticoagulants that interfere with the binding of phospholipid coagulation factors and prolong TP and TPT, but do not cause clinically obvious bleeding. The presence of lupus-specific anticoagulants may increase the risk of thromboembolism and may cause placental infarction and recurrent abortions in the second trimester of pregnancy. Some patients may develop inhibitors that are not antibodies. For example, in many patients with clinically obvious haemorrhage, circulating mucopolysaccharides with heparin-like activity have been described.
All right, that's enough for today! Anyway, after I complete everything I find useful, I will "complete" all the posts of The New Medicine, including this one, with new elements... But for the next time I'll move on to pathological changes in granulocytes and monocytes.
And this is going to be a slightly longer post because I want to finish this "group"...
I'll continue with the clinical evaluation, based on the history. Some elements of anamnesis are useful to determine whether a hemorrhage is caused by a disturbance of hemostasis or a local anatomical defect. A first element would be a history of hemorrhage after ordinary local trauma, such as a dental extraction, birth or minor surgery.
Hemorrhage large enough to require a transfusion requires special attention. A family history of bleeding or bleeding with multiple sites that cannot be explained by trauma or surgery also suggests a systemic condition. Since bleeding may be moderate, the absence of a family history does not exclude an inherited hemostasis condition. The defect can be located in platelets or plasma clotting system.
Hemorrhage due to platelet defects is usually superficial, localized in the skin and mucous membranes, occurs immediately after trauma or surgery and is easily controllable by local treatment. Hemorrhages that occur as a result of a defect in secondary hemostasis (plasma coagulation system) occur within hours or days of the injury and are not influenced by local therapy. This type of hemorrhage is most commonly located in the body's subcutaneous tissue, muscles, joints and cavities. A careful and meticulous history is probably the most important step in establishing the presence of a hemostasis disorder and guiding initial laboratory tests.
Associated with a careful history, the physical examination provides useful information for the evaluation of patients with hemostasis disorders. The most common location where hemorrhages can be observed is the skin and mucous membranes. Blood collections in the skin are called purple and can be classified according to the location of the haemorrhage. Small, punctual, intradermal haemorrhages, due to the extravasation of hematoids from the capillaries, are called spots and are characteristic for platelet defects, especially for severe thrombocytopenia.
Larger subcutaneous collections, due to the extravasation of blood from arterioles and small venus, represent bruising (bruising) or, if deeper and palpable, hematomas. They are common in patients with platelet defects and follow after minor trauma. There are other skin and mucous lesions, such as capillary dilation, telangiectasis, which can cause bleeding in the absence of any hemostasis disorders. In addition, the loss of connective tissue support for capillaries and small veins, which occurs with age, increases the fragility of superficial veins, such as those on the dorsal face of the hand, leading to the extravasation of blood in the subcutaneous cell tissue, senile purpura.
Menorrhagia is often a serious problem for women with severe thrombocytopenia or platelet dysfunction. In addition, patients with primary hemostasis disorders, especially those with von Willebrand disease, may have recurrent gastrointestinal bleeding. As mentioned above, bleeding in the serous, retroperitoneal or joint cavities is a frequent manifestation of plasma clotting deficits. Repeated joint bleeding can lead to thickening of the synovial, chronic inflammation, the appearance of fluid collections and can erode the articular cartilage, causing chronic joint deformities, with limitation of mobility.
Such deformities are present especially in patients with factor VIII and IX deficiency, the two sex-linked coagulation disorders, called hemophilias. For unclear reasons, hemarthrosis is uncommon in other defects of plasma coagulation. Blood collections in the serous cavities or soft tissues can cause secondary tissue necrosis or nerve compression. Retroperitoneal hematomas can produce compression of the femoral nerve, and collections of poorly coagulated blood in soft tissues can mimic a malignant transformation (pseudotumor syndrome). Hemorrhages in the oropharyngeal, where bleeding can compromise the normal functioning of the airways, and those in the central nervous system can be life-threatening. Intracerebral haemorrhages are one of the major causes of death in patients with severe clotting defects.
From the point of view of laboratory tests, the most important screening tests of primary hemostasis mechanisms are: 1. bleeding time (a sensitive indicator of platelet function) and 2. platelet count (this is very useful, being easy to achieve and correlates well with the predisposition to bleeding). Normal platelet levels are between 150,000 and 450,000 per cubic millimeter of blood. As long as the number of plaques is over 100,000 per cubic millimeter, patients remain asymptomatic and bleeding time is normal.
Patients with plaques below 50,000 per cubic millimeter experience rapid bleeding after concussions, manifested by skin purpura after minor trauma and bleeding after mucosal surgery. Patients with less than 20,000 platelets per cubic millimeter have a much increased incidence of spontaneous bleeding, usually have spots and may have intracranial or other spontaneous internal bleeding.
The main causes of thrombocytopenia are represented by: 1. decrease in medullary production of megakaryotes (a. infiltration of the marrow with tumors, fibrosis and b. medullary insufficiency in aplastic, hypoplastic or as an effect of taking drugs), 2. splenic sequestration of circulating plaques (a. hypertrophy of the spleen due to tumor infiltration and b. congestion of the spleen due to portal hypertension), 3. increased destruction of circulating plaques (a. non-immune destruction due to vascular prostheses, heart valves, disseminated intravascular coagulation, septicaemia or vasculitis and b. immune destruction due to autoantibodies to platelet antigens, antibodies associated with drug ingestion and circulating immune complexes as in the case of systemic lupus erythematosus, viral agents or bacterial septicaemia).
Patients with qualitative platelet abnormalities have a normal platelet count and a prolonged bleeding time. The disorders of primary hemostasis (of plaques) are represented by: 1. defects of platelet adhesion (with a. von Willebrand disease and b. Bernard-Soulier syndrome represented by the absence or dysfunction of glycoprotein Ib/ IX), 2. platelet aggregation defects (with Glanzmann thrombasthenia represented by the absence or dysfunction of glycoprotein IIb/ IIIa), 3. defects in platelet secretion (with a. decreased cyclooxygenase activity due to drugs such as aspirin and non-steroidal anti-inflammatory drugs or congenital cause, b. deficiencies in the deposits of granules with congenital or acquired causes and c. uremia resulting from platelet "coverages" caused, for example, by penicillin or paraprotein) and 3. platelet coagulation defects (as in the case of Scott syndrome).
The bleeding time is determined by practicing a small, superficial incision, and measuring the duration of bleeding in that area. Although it is a relatively simple "biotest", thanks to careful standardization, it has become a faithful and sensitive test of platelet function. The most widespread technique uses a type or automatic scalpel to control the length and depth of the incision (usually 1 mm deep and 9 mm long) and a sphygmanometer adjusted to 40 mmHg to evenly loosen the capillary bed in the forearm.
To be useful, bleeding time should be practiced by an experienced technician, as small differences in technique have a great effect on test results. Although any patient with a bleeding time of more than 10 minutes has a slightly increased risk of bleeding, this risk becomes significant only in patients with bleeding time values exceeding 15-20 minutes (there is an almost linear correlation between bleeding time and platelet count). When a deficiency of primary hemostasis is discovered, specialized tests are needed to determine the cause of platelet dysfunction.
An accurate diagnosis is important, as patients with bleeding due to primary hemostasis may require treatment with platelet mass, certain hormones (desmopressin, estrogens, glucocorticoids) or plasma fractions, depending on the nature of the condition. Occasionally, patients with a multiple history of bleeding, especially those with von Willebrand disease (mild form, may have a normal bleeding time on an initial test due to cyclic variations in von Willebrand factor levels). They require repeated testing to establish an accurate diagnosis.
Plasma coagulation function is easily evaluated using simple laboratory tests such as: partial thromboplastin time (TPT), prothrombin time (TP), thrombin time (TT) and quantitative determination of fibrinogen. TPT tests the intrinsic pathway of coagulation, assessing the effectiveness of factors XII, KGMM, PK, XI, IX and VIII. TP tests the extrinsic pathway, dependent on the tissue factor. Both tests assess the common coagulation pathway, involving all reactions that occur after the activation of factor X.
Prolongation of TPT and TP that is not corrected after the addition of normal plasma suggests the presence of a clotting inhibitor. When both TPT and TP are prolonged, it becomes necessary to use a specific test to assess the conversion of fibrinogen into fibrin (either TT or fibrinogen level determination can be used). When abnormalities are found in any of these tests, more specific investigations of coagulation factors may be required to determine the nature of the defect. There are a few rare coagulation abnormalities that may remain undetected because they do not alter the screening tests discussed.
These are factor XIII deficiency, plasmin alpha2 inhibitor deficiency, PAI-1 deficiency (which is the most important plasminogen activator inhibitor) and Scott syndrome, a platelet coagulation defect. A test for fibrin polymerization (dependent on factor XIII), such as clot solubility in 5-M-urea, should be requested when TP and TPT are both normal, but there is a history of frequent bleeding.
The fibrinolytic system can be investigated by measuring the lysis time of the euglobulin clot or total blood clot and for measuring the alpha2 inhibitor levels of plasmin and IAP-1. Scott syndrome can be diagnosed by measuring prothrombin time, which assesses the amount of residual prothrombin.
Diseases associated with thrombosis are: A. congenital (with 1. deficient inhibition of clotting factors: a. factor V Leiden - resistant to inhibition by activated protein C, b. antitrobin deficiency III, c. protein deficiency C, d. protein deficiency S, 2. altered clot lysis with a. disfibrinogenemia, b. plasminogen deficiency, c. tAP deficiency , d. excess PAI-1 and 3. with uncertain mechanism - as is the case with hemocystinuria) and B. acquired (with 1. diseases or syndromes with a. lupus anticoagulant, b. malignancies, c. myeloproliferative diseases, d. thrombocytopenic purpura, e. estrogenic treatment, f. hyperlipemia, g. diabetes mellitus, h. hyperviscosity, i. nephrotic syndrome, j. congestive heart failure and k. nocturnal paroxysmal hemoglobinuria and 2. , b. obesity, c. postoperative states, d. immobilization and e. old age).
There are no clinical screening tests for patients suspected of having hypercoagulability or prethrombotic disorders. In the research laboratories, tests have been developed that measure peptides of low molecular weight or complexes that inhibit enzymes generated during coagulation. For example, radioimmunological tests have been developed for fibroids A and B, thrombin-antithrombin complex and prothrombin cleavage fragments. Increased levels of these products have been reported in patients with prethrombotic or thromboembolism.
Currently, patients suspected of being hypercoagulable based on clinical data should undergo specific tests for the few defects currently known. Currently available tests can identify 10-20% of cases of familial thrombosis, which represent a small proportion of patients who report to the doctor with thromboembolic phenomena. Inhibitory syndromes or circulating anticoagulants are usually due to antibodies that decrease the activity of clotting factors. It is not a common cause of hemorrhage, and requires specific diagnostic tests.
The presence of inhibitors is likely when changes in screening tests cannot be corrected by adding normal plasma to the patient's plasma. Specific antibodies against coagulation factors may be present: 1. postpartum, 2. in patients with autoimmune diseases, such as systemic lupus erythematosus, 3. in patients using drugs such as penicillin or streptomycin and 4. in elderly patients without other diseases. In addition, of patients with severe haemophilia who have received multiple transfusions, 10 to 20% develop inhibitory antibodies.
Some patients, especially those with systemic lupus erythematosus, may have non-specific anticoagulants that interfere with the binding of phospholipid coagulation factors and prolong TP and TPT, but do not cause clinically obvious bleeding. The presence of lupus-specific anticoagulants may increase the risk of thromboembolism and may cause placental infarction and recurrent abortions in the second trimester of pregnancy. Some patients may develop inhibitors that are not antibodies. For example, in many patients with clinically obvious haemorrhage, circulating mucopolysaccharides with heparin-like activity have been described.
All right, that's enough for today! Anyway, after I complete everything I find useful, I will "complete" all the posts of The New Medicine, including this one, with new elements... But for the next time I'll move on to pathological changes in granulocytes and monocytes.
As usual, I wish you well
and understanding, love and gratitude!
Dorin, Merticaru