​Causes of poor blood clotting, diagnosis and treatment methods

General information

The blood coagulation system is a complex sequential cascade of reactions occurring in the body that is aimed at stopping bleeding. The coagulation process is an important protective reaction of the body, thanks to which a constant volume of circulating blood is maintained. homeostasis system involves many components, the main ones of which are shown in the figure below.
Clotting factors are in an inactive state in the blood. If a blood vessel is injured, the coagulation process begins and all factors are sequentially activated and ensure the formation of a clot. The direct coagulation process itself is associated with the conversion of the fibrinogen protein (factor I) into insoluble fibrin.

Coagulopathy is a disease, or rather a group of diseases or conditions, which are based on a blood clotting disorder. The clinical sign of coagulopathy is bleeding. Acquired coagulopathies are the most common syndromes. In this case, poor blood clotting can be caused by pathology of different parts of the coagulation system: fibrin , platelets or blood clotting factors . If any part of this system does not function or is missing, the person will have prolonged bleeding and develop a critical condition. Among coagulopathies there are congenital conditions and diseases ( hypofibrinogenemia (factor I deficiency), afibrinogenemia , hemophilia A , von Willebrand disease , hemophilia B ) and acquired syndromes that occur in various septic conditions and diseases of the kidneys and liver.

What to do if blood doesn't clot well

If you have the symptoms listed above, you should definitely consult a doctor and undergo an examination. At the moment of bleeding itself, first aid should be provided in accordance with general recommendations, based on the location and type of injury. If necessary, call an ambulance.

Diagnostics

To diagnose blood clotting, the doctor first reviews the patient's medical history. To do this, he will ask questions about your health problems and medications you are taking. You need to answer something like this list of questions:

• What are the accompanying symptoms?
• How often does bleeding occur?
• How long does the bleeding last?
• What were you doing before the bleeding started (for example, were you sick, took medications)?

Basic tests to check blood clotting :

• A complete blood count to check the blood loss at the time the test was taken and the number of red and white blood cells.
• Platelet aggregation test, which shows the extent to which platelets are able to adhere to each other.
• Measuring bleeding time to see how quickly blood vessels clog after pricking a finger with a feather.

Treatment options for poor blood clotting

Treatment for a bleeding disorder is based on the causes that cause it. If possible, the diseases that caused the disorder, such as cancer or liver disease, are immediately treated. Additional treatments include:

• Taking vitamin K by injection;
• Drugs aimed at improving clotting function;
• Transfusion of frozen donor blood plasma or donor platelets;
• Other drugs, including hydroxyurea (Droxia, Hydrea), and oprelvequin (Neumega) to treat platelet-related disorders.

Treatment of consequences caused by blood loss

Iron supplements

If there is significant blood loss, the doctor may prescribe medications containing iron to replenish its amount in the body. Low iron levels can lead to iron deficiency anemia, which is accompanied by feelings of weakness, shortness of breath and dizziness. One of the most common and accessible drugs in this case is Hematogen. In addition to treatment with iron supplements, blood transfusions may be required.

Blood transfusion

During this procedure, as most people know, blood loss is compensated with the help of donor blood. Donated blood must match your blood type to prevent complications. This procedure can only be performed in a hospital.

Pathogenesis

The pathogenesis of hemorrhagic syndrome includes:

• damage to vascular endothelial cells by inflammatory mediators or endotoxin ;
• activation of protein C , which inhibits FV and FVIII and suppresses the synthesis of plasminogen activator inhibitor (the latter promotes the transition of plasminogen to plasmin, which breaks down the fibrin of the blood clot);
• activation of fibrinolysis, which plays a role in the development of non-stop bleeding and depletion of f I, II, V, VIII, XIII;
• accumulation in the blood of metabolites that have an anticoagulant effect.

In the pathogenesis of uremic thrombocytopathy, platelet deficiency is important, which is associated with the action of toxic plasma metabolites. In addition, patients with uremia undergo an extracorporeal circulation procedure, in which platelet dysfunction occurs due to their interaction with the tubes and membranes of the device. In this case, platelets are activated and release granules (platelet degranulation). Platelet dysfunction causes bleeding so severe that platelet transfusion is required.

Drug-induced thrombocytopenia is associated with the interaction of the drug (or its metabolite) and a platelet membrane glycoprotein. As a result of this interaction, an immunogenic complex - a glycoprotein-drug . Altered platelets are removed from the bloodstream by RPE cells. With drug-induced thrombocytopenia, the level of IgG and platelet-bound antibodies to the drug increase. Idiopathic purpura based on the production of antibodies against viral antigens. Platelets are damaged by adsorbing a viral antigen or a virus-antibody immune complex on their membrane.

On the operating table

— How can a person suspect he has thrombosis?

— Clinical manifestations of thrombosis occur not only against the background of Covid. It can develop after surgery, serious trauma, when taking oral contraceptives, chemotherapy, etc. Acute venous thrombosis is characterized by sudden swelling, constant bursting pain in the limb, cyanosis or redness of the skin of the legs.

It should be noted that quite often clinical manifestations due to thrombosis may be absent or of a low-symptomatic nature. On the other hand, with chronic diseases of the veins of the legs, heaviness in the lower extremities, swelling and pain, cramps, parasthesia (burning sensation, tingling, “pins and needles”) are often observed, and in more severe situations – trophic disorders and pigmentation.

The extreme degree is a venous trophic ulcer. More often it occurs on the inner surface of the lower leg. However, modern medical capabilities make it possible to successfully treat this condition.

Legs.

news.rambler.ru

As for pulmonary embolism, it may be symptomatic or not manifest itself at all. With massive damage and blockage of the blood vessels of the lungs, a person’s blood pressure seriously decreases, severe shortness of breath and palpitations appear, and loss of consciousness may occur.

This is a life-threatening condition that requires emergency hospitalization and inpatient treatment in a specialized vascular center. It is very dangerous.

It must be said that thromboembolism also occurs in inpatients after surgical interventions - in urology, gynecology, oncology. In approximately 10% of cases, this is, so to speak, “pure” thromboembolism, which is associated with the development of thrombosis directly in the vessels of the lungs, and in the rest it is a consequence of existing thrombosis of the deep veins and inferior vena cava.

Operation.

Oncology Center.

- Why is this happening?

— There are many risks of getting thrombosis in the early postoperative period and even right on the operating table. This is facilitated by the operation itself, bed rest, dehydration, excess body weight, etc. The older the patient, the higher the possibility of thrombosis. This is influenced by the duration and nature of the operation itself: if it is performed openly and not using minimally invasive technologies, then the risks are higher.

There are global and Russian recommendations for assessing these risks. For example, the Caprini scale. It takes into account everything from heart disease, previous surgeries to age, pregnancy and injuries that the patient has ever had - more than two dozen parameters, for each of which points are awarded. New important risk factors are now being added to this scale.

The higher the risk of developing venous thrombosis, the more attention is paid to prevention. It is simple - a normal drinking regime for the patient, activation and getting to the feet as early as possible after surgery, administration of anticoagulants (to “thin” the blood) and mandatory wearing of compression stockings (stockings, elastic bandages). All this accelerates blood flow in the deep veins so that there is no stagnation of blood in the lower extremities and pelvis.

Doctors. Operation.

CCO.

Classification

Coagulopathies are divided into hereditary and acquired.

• Hereditary forms are associated with genetically determined changes in the walls of blood vessels, abnormalities of platelets and plasma blood factors. Hereditary coagulopathies include hemophilia A , von Willebrand disease , hemophilia B , and deficiency of various clotting factors.
• Acquired forms are most often associated with vascular damage of various etiologies (immune, toxicoinfectious and dysmetabolic), platelet damage, pathology of coagulation factors and a combination of all these factors.

The following types of acquired coagulopathy are distinguished:

• Disorders of platelet hemostasis . These include thrombocytopenia of various origins (associated with decreased platelet production, associated with increased platelet destruction, caused by non-immune causes and immune ones - idiopathic thrombocytopenic purpura), HELLP and hemolytic-uremic syndrome, thrombotic thrombocytopenic purpura, thrombocytopathies. With thrombocytopenia, the platelet germ may be primarily affected, platelets can be redistributed and accumulate in the spleen, and there will be an insufficient number of them in the blood. Also, platelets can be destroyed in large quantities (with lupus erythematosus and thrombocytopenic purpura). In addition, platelets can be consumed in large quantities during the formation of blood clots (for example, in DIC syndrome). Thrombocytopathies are characterized by the production of abnormal platelets whose function is impaired. An example of thrombocytopathy is von Willebrand disease and Glanzmann thrombasthenia .
• Types of coagulation disorders. This group includes hemostasis disorders associated with an overdose of anticoagulants ( heparin , warfarin ), hemodilution coagulopathy , vitamin K-dependent (with impaired liver function, poor absorption of vitamin K, taking certain medications).
• Coagulation-platelet (mixed) disorders that developed against the background of liver and kidney failure (hepatic and uremic coagulopathy).
• DIC syndrome is distinguished separately.

Fibrinogen plays an important role in the blood coagulation system . Normally its content is 2-4 g/l. Patients often have hypofibrinogenemia —a decrease in fibrinogen levels. This condition can be hereditary, but more often acquired, due to insufficient formation of this liver protein when it is damaged or its increased dissolution (fibrinolysis). In this condition, blood clotting slows down and as a result, a loose, disintegrating clot is formed. Hypofibrinogenemia manifests itself through the formation of bruises with minor trauma and various bleeding.

However, in most patients, decreased fibrinogen levels do not manifest themselves in any way. A decrease in the level of this protein is observed in cirrhosis , liver necrosis , bone marrow metastases leukemia , shock , anemia , eclampsia , premature placental abruption, complicated childbirth, and sepsis. The cause of acute hypofibrinogenemia is intravascular coagulation when fibrinogen is intensively consumed. Many patients with low fibrinogen levels do not require treatment. Heavy menstruation in women is prevented by hormonal agents and antifibrinolytic drugs.

Afibrinogenemia is a complete absence of fibrinogen in the blood with a normal platelet level. This is a genetically determined disease, but is very rare. In this condition, any injury leads to bleeding, hematomas, and hemorrhages in the joints. Dental manipulations and operations are accompanied by significant blood loss. Children rarely survive to adulthood. In the treatment of this pathology, replacement therapy is used: administration of fibrinogen , cryoprecipitate and fresh frozen plasma .

Blood clotting

Many people begin to fear blood clots after, when donating blood from a vein, the nurse reports that it is too viscous. Those who have too thin blood that successfully fills the test tube hope that they are protected from thrombosis. But viscosity and coagulability are two completely different concepts, and one does not always determine the other.

How viscous you are

Increased blood viscosity, due to which it becomes less fluid, most often occurs due to the predominance of its formed elements over liquid ones. This happens due to too strict adherence to the recommendations “do not eat 12 hours before taking the test” and because of the decision to add one more restriction to this – not to drink. Just to be sure. The end result is worse - and the blood flows poorly into the test tube, and some indicators (for example, hemoglobin, hematocrit, total number of red blood cells, white blood cells and platelets) turn out to be artificially high. Therefore, it is important to remember: before taking blood tests, you should not limit yourself to fluids.

Another common cause of increased viscosity is increased levels of red blood cells and hemoglobin, characteristic of smokers. After all, the more smoke and less air a person inhales, the greater the concentration of oxygen carriers required. Their compensatory increase is formed. Therefore, visually, the blood of smokers often appears more viscous.

According to hematologists, true diseases (thrombocytosis, erythrocytosis, etc.) associated with increased blood viscosity account for a small number of all cases of “viscous blood”. And this is clearly visible from a routine general blood test - the doctor will immediately notice that the number of red blood cells or platelets is too high.

Normally, the content of red blood cells is 3.7-5.1, platelets - 180-320.

Viscosity and coagulability - what's the difference?

The most important indicator is blood clotting. Unfortunately, it can be difficult to obtain accurate information about coagulation, even despite the level of development of medicine. On the one hand, obvious diseases with clotting disorders, such as hemophilia, have long been known. On the other hand, there is a lot of hidden pathology, which may not show itself for a long time, but once manifested, it can quickly lead to serious consequences.

Only in recent decades have researchers learned to identify these problems using high-tech genetic tests. Considering that, according to statistics, more than 1-3% of the world's population has a congenital pathology of the blood coagulation system, it is likely that in the future these tests will be carried out in the maternity hospital for every newborn. And absolutely for those who need to be prescribed certain medications that can increase the risk of blood clots.

Protection or danger?

For example, this is very important to do before prescribing hormonal contraceptives. Their ability to enhance blood clotting and occasionally lead to thrombosis (as it turns out, this almost always occurs in women who have a hidden clotting disorder) has been known for several decades. Due to the widespread use of this method of protection against unwanted pregnancy these days, the incidence of thrombosis in young, apparently healthy women has increased. At the same time, when prescribing COCs, gynecologists rarely focus their patients’ attention on this danger. They can be understood - the complication is infrequent in general, and I don’t want to once again intimidate patients, as if pushing them into an unwanted pregnancy. Meanwhile, the most advanced Western colleagues have already included a full blood clotting test in the mandatory examination algorithm before prescribing hormonal contraceptives.

What will the analysis show?

What tests need to be done to check blood clotting? The most common and familiar analysis to many, a coagulogram, may not answer all questions, especially in the prevention of thrombosis.

However, a classic coagulogram is the first stage of a screening examination of the coagulation system. If it reveals abnormalities, the next step will be more detailed studies of hemostasis - thromboelastography or thromboelastometry. A separate story is the determination of D-dimer , Leiden mutation and other genetic clotting disorders - tests that reveal a tendency to form blood clots in the future. What is necessary and in what cases?

The most common standard coagulogram today includes five components: PTI (prothrombin index); INR (International Normalized Ratio. Reflects the ratio of the patient’s blood clotting time to the blood clotting time of a healthy patient; APTT (activated partial thromboplastin time. Estimates the time it takes for a blood clot to form after special reagents are added to the plasma), FIBROGEN and PLATELET LEVEL.

At the same time, APTT is informative only in people undergoing treatment with heparin, and INR is important only for people constantly taking blood-thinning drugs from the neodicoumarin group (warfarin).

It turns out that two out of five indicators are not so important for screening. The total number of platelets is also not always indicative, because with most coagulopathies it is not their number that changes, but primarily the functional activity.

Therefore, the most informative method, which allows one to evaluate several stages of blood coagulation at once, is thromboelastography. This is a kind of detailed observation of the formation of a blood clot, and its subsequent dissolution (lysis) with the construction of graphs of each of the stages. Thromboelastometry is another version of this study, which is considered even more informative. Unfortunately, the instruments for conducting these studies are expensive and require special training of personnel, so not every laboratory can offer thromboelastography services.

Another important indicator is D-DIMER (this is a breakdown product of fibrin, a small fragment of protein present in the blood after the destruction of a blood clot).

It is actively used to determine the risk of blood clots. Those with even slightly elevated D-dimer are at much greater risk of developing blood clots than others. It is necessary to monitor D-dimer in case of venous diseases (thrombophlebitis), after surgical interventions and upon discharge from the hospital if you have been bedridden for a long time. Monitoring D-dimer levels is useful during pregnancy and when taking hormonal contraceptives (the risk of blood clots in the presence of the Leiden mutation while taking birth control pills increases almost 9 times). And now during COVID-19 and several weeks after recovery.

Today, in addition to D-dimer testing, genetic tests for congenital bleeding disorders are emerging. The most common of these is the Leiden mutation, which occurs in 2–6% of Europeans. The presence of a defective gene increases the likelihood of venous blood clots 6–8 times, and the risk of heart attack and stroke increases significantly. But other mutations, of which there are more than ten today, are no less dangerous. At the same time, timely prevention of thrombosis (mainly the constant use of anticoagulants, the exclusion of certain foods and medications, wearing compression stockings when flying and working on your feet, etc.) reduces the risk of dangerous complications tenfold.

Flickering problem

If everything is in order with the coagulation system, a possible cause of increased coagulation may be arrhythmia, namely atrial fibrillation. According to statistics, 2% of the planet's population suffers from paroxysmal (occurring in attacks) or permanent form of atrial fibrillation. This problem usually appears after thirty. The basis for the disorder is the appearance of pathological turbulence of the electrical impulse in the atria, which gives the myocardium extraordinary electrical stimuli. In medical language, this is called the “re-entry” or re-entry mechanism. As a result, the atria become a churn that churns blood into clots like milk into butter. The situation worsens even more in the case where the person initially had the same clotting disorders. Blood clots can form within 48 hours after the onset of an attack and “fly away” into the arteries of the brain, causing an ischemic stroke, into the intestines, leading to mesenteric thrombosis, into the arteries of the extremities, provoking their acute ischemia.

Von Willebrand factor and COVID -19.

Severe COVID-19 may be associated with elevated levels of one of the blood coagulation factors, von Willebrand factor. Anna Aksenova, a senior researcher at the Laboratory of Amyloid Biology at St. Petersburg State University . Her scientific article was published in the journal Ecological Genetics. It has already been proven that the SARS-Cov-2 virus can have a direct damaging effect on the inner wall of blood vessels. In response to damage, the body strives to “patch” the hole as quickly as possible, and the leading role in this is played by the von Willebrand factor, which is involved in the activation of platelets and, in fact, triggers the process of local thrombus formation. In the course of research, it turned out that some people are characterized by an increased concentration of this factor in their cells, so, as a rule, it is higher in people with blood group II. An individual characteristic of the body is also possible. As a result, in response to massive microdamage to blood vessels, massive microthrombosis occurs, which causes the appearance of larger and more dangerous blood clots.

Genetic mutations of the coagulation system identified during tests:

MUTATION OF COAGULATION FACTOR V OF BLOOD CLOTTING (LEIDEN FACTOR)

PLASMINOGEN ACTIVATOR INHIBITOR 1

MUTATION OF COAGULATION FACTOR II (MUTATION OF PROTHROMBIN)

MUTATION OF METHYLENETETRAHYDROPOLATE REDUCTASE (MTHFR C677T)

MUTATION OF COAGULATION FACTOR VII OF BLOOD CLOTTING (F7 ARG353GLN)

POLYMORPHISM OF THE METHIONINE SYNTHASE REDUCTASE GENE (MTRR A66G)

FIBRINOGEN MUTATION, BETA (FGB G-455A)

MUTATION OF THE PROMOTER OF THE COAGULATION FACTOR GENE FVII (-312 INS 10BP)

INSERTATION/DELETION OF ALU ELEMENT IN THE ANGIOTENSIN CONVERTING ENZYME GENE (ALU INS/DEL)

PLATELET GLYCOPROTEIN 1B ALPHA SUBUNIT MUTATION

PLATELET ADP RECEPTOR MUTATION (P2RY12 H1/H2)

MUTATION A1298C OF METHYLENETETRAFOLATE REDUCTASE GENE

D-dimer is significantly elevated in most patients with moderate to severe COVID-19. Therefore, all patients receive therapeutic doses of anticoagulants.

The Leiden mutation is the most common hidden bleeding disorder, occurring in 2-6% of Europeans.
Published: January 19, 2022

Causes of poor blood clotting

Based on the above, we can name the main causes of coagulation disorders:

• Vascular wall defects are hereditary (associated with collagen abnormalities) and acquired (immune or inflammatory vascular lesions).
• Pathology of platelets. Platelet dysfunction sometimes causes significant bleeding. It includes thrombocytopenia (quantitative changes in platelets) and thrombocytopathies (changes in platelet quality). Acquired thrombocytopathies are caused by taking non-steroidal anti-inflammatory drugs, dipyridamole , antibiotics , uremia , heart valve pathology, and the use of extracorporeal circulation.
• The cause of a bleeding disorder may be a lack of factors (there are thirteen of them) of the blood coagulation system or a reduced synthesis of one or more factors. Prothrombin (factor II) is the main component of blood clotting. It is a precursor of thrombin and is involved in the formation of a clot (thrombus). Fibrinogen (factor I) is produced in the liver. In the coagulation cascade, it is converted into fibrin, which participates in clot formation. The deficiency of this factor was mentioned above.
• Deficiency of factor XI is associated with hemophilia C, factor VIII with hemophilia A , and factor IX with hemophilia B. Among hereditary coagulopathies, the most common (in 95% of cases) deficiency of factors VIII and IX. Deficiency of factors VII, X, V, XI is only 1.5%. Acquired deficiency of prothrombin complex factors (II, VII, X, V) occurs in liver diseases, jaundice , dysbacteriosis , as well as in overdose of vitamin K .
• The cause of bleeding can also be increased fibrinolysis , that is, excessive fibrinolytic activity. This may be a hereditary deficiency of alpha2-antiplasmin or increased formation of plasminogen activators and impaired excretion of these activators in liver diseases.

Disorders of vascular-platelet hemostasis

Disturbances in this part of hemostasis most often manifest themselves as increased bleeding, a tendency to form hematomas (bruises) with the slightest contact, or even spontaneously, for no apparent reason. In some situations, on the contrary, there is a tendency to excessively easy thrombosis.

There are factors that stimulate the formation of a primary thrombus and those that disrupt it. Stimulants include the inflammatory process, because inflammation increases the content of biologically active substances in the blood. We can say that there is a readiness for the formation of a blood clot; it is only a matter of local damage to the vessel. Therefore, in severe infectious diseases, blockage of blood vessels may occur. There is an increased readiness for thrombosis during pregnancy, as well as in some hereditary diseases (thrombophilia). Among food products, table vinegar (marinades) and coffee increase platelet activity.

The process of formation of a primary thrombus is disrupted when the number of platelets decreases (thrombocytopenia) and when there is a qualitative deficiency of platelets (thrombocytopathy). Thrombocytopathy can occur when taking certain medications. First of all, these are anti-inflammatory drugs: aspirin, analgin, brufen, some antibiotics. Thrombocytopathy also develops in kidney diseases. Spices and strong alcohol can also reduce the usefulness of platelets.

The blood coagulation system is actually several interconnected reactions occurring in the form of a cascade, or chain reaction. At each stage of this process, the proenzyme (the inactive form of the enzyme) is activated. Thirteen of these proteins (clotting factors) make up the coagulation system. They are usually designated by Roman numerals from I to XIII.

Symptoms

Whatever the cause of coagulopathy, the main symptom is bleeding of varying severity - from small bruises to severe bleeding during injuries (including minor ones). On the skin side, patients experience small petechiae , hematomas , bruises at injection sites, nasal and gingival bruises, heavy uterine bleeding in women, and often gastrointestinal bleeding.

Thrombocytopathies , both congenital and acquired, are not accompanied by severe hemorrhages . Bleeding in such patients can develop only during operations, injuries and tooth extraction. The most common manifestations are bruising and periodic nosebleeds and gum bleeding.

Thrombocytopenic purpura is a very common disease, especially among women 20-30 years old. Patients develop petechiae , bloody blisters that rise above the skin, bleeding gums and heavy uterine bleeding. The disease begins either gradually or acutely with hemorrhagic syndrome. According to its manifestations, there are two types of purpura: “wet”, when hemorrhages are combined with bleeding, and “dry”, if the patient has only skin hemorrhages. Hemorrhagic syndrome on the skin is observed in 100% of patients.

The number of hemorrhages can be single or multiple. Cutaneous hemorrhagic syndrome is characterized by:

• Various hemorrhagic rashes - petechiae and large hemorrhages.
• Inconsistency of hemorrhages with the degree of injury.
• Spontaneous appearance at night.
• Different colors of skin hemorrhages depending on the age.
• Painless.
• Asymmetry of elements.
• Hemorrhages in the soft palate and tonsils, sclera, fundus. Scleral hemorrhage sometimes precedes severe cerebral hemorrhage, which occurs quickly and progresses.
• Manifested by dizziness , headache , convulsions .

With von Willebrand disease, there is a tendency to intradermal hemorrhages, effusions of blood into the mucous membranes and severe bleeding after injury.

Tests and diagnostics

Coagulological screening includes:

• prothrombin index;
• activated partial thromboplastin time;
• amount of fibrinogen;
• platelet count;
• bleeding time.

In case of isolated prolongation of activated partial thromboplastin time, proceed to the second stage of examination:

• do a correction test;
• activity of factors VIII, IX, XI, XII.

If the activity of factor VIII decreases, they proceed to the third stage of examination:

• lupus anticoagulant;
• specific inhibitor of factor VIII.

In children

Poor blood clotting in a child is often associated with immune thrombocytopenic purpura . Acute purpura develops between the ages of 2 and 9 years. This is an immune-related disease characterized by a constant (or periodic) decrease in platelets of less than 100 thousand. The disorder in children occurs 1-3 weeks after a viral infection. Such pathological reactivity can start not only under the influence of a viral infection, but also after taking medications, vaccination, exposure to temperatures (both low and high), surgical interventions or emotional stress. Against the background of normal health, the child develops a petechial rash (on the mucous membranes and skin), bruises, repeated nosebleeds and bleeding gums. In severe cases, there may be brain hemorrhages and stomach bleeding. Since antigens gradually leave the blood, in most people the disease goes away on its own after 2 months.

Vitamin K deficiency coagulopathy occurs in children in the first months of life and newborns . With Vit-K deficiency, the activity of several factors decreases: prothrombin , proconvertin , Christmas factor and Prower factor . hypocoagulation develops , accompanied by hemorrhagic syndrome.

Causes of Vit-K deficiency in a newborn:

• taking anticoagulants during pregnancy;
• antibiotics;
• anticonvulsants;
• severe damage to the pregnant woman’s liver and intestines;
• the presence of fetoplacental insufficiency;
• gestosis and preeclampsia .

The manifestations of this coagulopathy in newborns are not very specific - skin syndrome, increased bleeding during blood sampling and bleeding from the umbilical wound. With a lack of Vit-K, the duration of bleeding and platelet levels are within normal limits. Many authors recommend prophylactic administration of Vit K to all children immediately after birth - 2-3 administrations for the first 1.5 months, and in some cases weekly administration continues up to 3 months.

In later life, Vit-K deficiency coagulopathy is caused by breastfeeding only. At the same time, 78% of children develop massive intracranial hemorrhages. Much less frequently, the cause of decreased coagulability in children is disseminated intravascular coagulation syndrome in severe sepsis, congenital metabolic changes and hereditary coagulopathies.

Poor blood clotting during pregnancy

A normal pregnancy is always accompanied by important biochemical changes, including in the hemostatic . However, there are pathological conditions that lead to blood clotting disorders. Coagulopathy in pregnancy, what is it? This is a pathological condition that occurs with impaired coagulation and an increased risk of bleeding.

Pathological bleeding in pregnant women can be caused by:

• Congenital disorders in the coagulation system.
• Werlhof's disease.
• Moschkowitz disease.
• Antithrombin deficiency , which often occurs during pregnancy.
• Preeclampsia.
• Eclampsia.
• DIC syndrome associated with preeclampsia. At the first stage, intravascular coagulation occurs, and then the coagulation system is depleted.
• HELLP syndrome, which is also associated with preeclampsia (hemolysis, elevated liver enzymes and thrombocytopenia). Disseminated intravascular coagulation syndrome, a combination of thrombosis and bleeding.
• HELLP syndrome combines a triad of manifestations: hemolysis , decreased platelet levels and increased liver enzymes. During pregnancy with severe preeclampsia, the frequency of this syndrome reaches 20%.
• It develops during full-term pregnancy, premature birth and even after childbirth. HELLP syndrome is considered a subtype of preeclampsia. Diagnostic criteria for this syndrome: platelets less than 100×10 in 9/l, transaminases 2-3 times higher than normal, hemolysis of erythrocytes, bilirubin more than 20.5 µmol/l.

Women experience nausea , swelling and pain in the right hypochondrium. Pregnant women with HELLP syndrome are prescribed magnesium sulfate before and after birth for two days. Platelet transfusion is indicated when platelets are less than 20 × 10 in 9/L if a natural birth is expected and when platelets are less than 50 × 10 in 9/L if a cesarean section . Thromboconcentrate is administered before delivery. Corticosteroids increase platelet levels, so their use is reasonable. In the postpartum period, plasma exchange is used.

In DIC syndrome, a short phase of hypercoagulation is replaced by hypocoagulation. Such changes occur if a woman loses 15-20% of her blood volume. In case of bleeding, a platelet concentrate is infused.

In case of bleeding and if the prothrombin time and activated thromboplastin time are increased, an infusion of fresh frozen plasma is performed. If it is not possible to administer plasma, clotting factor concentrates are administered. Severe hypofibrinogenemia , which is not corrected by plasma transfusion, is then transfused with cryoprecipitate . For hyperfibrinolysis and bleeding, tranexamic acid . Hemolytic-uremic syndrome in women is accompanied by thrombocytopenia , kidney damage and microangiopathy . This condition most often develops after childbirth. Plasma exchange in this pathology is not very effective - the woman requires hemodialysis .

Disturbances in the coagulation system

A decrease in the content or activity of coagulation factors may be accompanied by increased bleeding (for example, hemophilia A, hemophilia B, von Willebrand disease). Excessive activation of coagulation hemostasis (for example, Leiden mutation of factor V) leads to the development of thrombosis (thrombophilia).

Hemostasis and pregnancy

Among all the causes of miscarriage, problems in the hemostatic system are in second place in frequency. Second after obstetric and gynecological reasons. What's the matter?

During pregnancy, the expectant mother's body prepares for childbirth. The hemostasis system is also being prepared to minimize blood loss during childbirth. Hemostasis is activated progressively along with increasing gestational age. If a woman’s hemostasis is initially overactive, then during pregnancy microthrombi may form in the vessels of the uterus or placenta, which leads to miscarriage or frozen pregnancy.

Under what conditions can this happen?

1. 1. For hereditary thrombophilia,

   more often when there is a violation of the metabolism of folic acid and its compounds (folates), when the amount of homocysteine ​​in the blood increases. The reasons for the increase in homocysteine ​​levels may be a lack of folic acid and vitamin B12 in the diet, thyroid disease, and kidney disease. It can also increase in smokers, coffee drinkers and while taking medications such as theophylline (by the way, a relative of caffeine), nicotinic acid. Homocysteine ​​damages the endothelium (inner layer) of blood vessels, and this damage triggers blood clots.

2. 2. For antiphospholipid syndrome (APS)

   – this is the name of an autoimmune disease in which antibodies are produced to one’s own clotting factors. As a result, blood clots also spontaneously form in the vessels.

Prevention

It is impossible to influence congenital pathologies of the coagulation system, but people with such pathologies can take a more careful approach to their health, choice of profession and physical activity. Secondary prevention includes the following:

• Avoid physical activity associated with the possibility of getting bruised (sports, football, wrestling, figure skating, etc.).
• Oral hygiene that helps reduce the need for dental procedures and surgeries.
• Normalize weight, which puts stress on the joints and increases the risk of bleeding into the joint cavity.
• Avoid the use of medications that affect clotting. Among such drugs are acetylsalicylic acid , Clopidogrel , Caffeine , Ibuprofen , Naproxen , nitrofurans , barbiturates , carbenicillin .
• Women with congenital factor deficiencies should consult and be examined by a geneticist and find out the risks of having a child with a congenital blood clotting disorder.

Similarly, there is no primary prevention of thrombocytopenic purpura , and secondary prevention is limited to preventing exacerbations. Patients should not be exposed to the sun; they are contraindicated from working in conditions of elevated temperature (hot shop, food shop near the stove). Children are exempt from physical education. After each case of ARVI, it is mandatory to test the blood.

Reasons for the development of pathology

The mechanism and type of inheritance of hemophilia have been studied in sufficient detail. Genes that provoke insufficient production of blood clotting factors are linked to the X chromosome. The pathology is inherited recessively through the female line. Hereditary pathology occurs exclusively in boys.

The sons of a healthy man and a woman who is a carrier of the pathological gene are equally likely to be born without signs of hemophilia or with them. A man suffering from bleeding disorders will be able to conceive healthy children with a woman who is not a carrier of the altered gene.

Medicine knows of isolated cases of hemophilia in women. Their mothers were carriers of a mutated gene, and their fathers suffered from insufficient production of blood clotting factors. The cause of hemophilia in such cases is a combination of recessive and dominant genes.

Consequences and complications

With coagulopathies, the following complications may occur with varying probability and severity:

• Anemia.
• Hematuria (blood in the urine).
• Heavy and prolonged periods.
• Brain hemorrhage
• Gastrointestinal bleeding.
• Hemorrhage into the structures of the eye, pleurisy, compression of the larynx and trachea by hematomas.
• Hemorrhage into the joints and, as a consequence, the development of arthritis , arthrosis , osteoporosis and posthemorrhagic bursitis .
• Intravertebral hemorrhages.
• In rare cases, death due to massive bleeding.

Forecast

Acute forms of idiopathic purpura disappear within a few months and it often happens that the disease does not recur. In the chronic form, it is possible to induce remission, but the disease often recurs.

When using modern medications and following all recommendations for lifestyle changes and employment, thrombocytopenic purpura has a favorable prognosis.

Untreated hemophilia Lack of treatment often leads to joint pathology ( hemophilic arthropathy ), which then requires the use of crutches and wheelchairs or special orthopedic treatment. During treatment, life expectancy is practically no different from healthy individuals.

List of sources

• Fatkullin I.F., Zubairov D.M. Hereditary and acquired defects of the hemostatic system in obstetric and gynecological practice. M., 2002. P. 64.
• Galstyan G.M., Sukhanova G.A. Introduction to hemostasis, modern blood products and their effect on coagulation // Medical Council. 2013. from 11-13.
• Barkagan Z.S. Diagnosis and controlled therapy of hemostasis disorders / Z.S. Barkagan, A.P. Momot. – M.: Newdiamed, 2001. – 296 p.
• Barinov S.V., Dolgikh V.T., Medyannikova I.V. Hemocoagulation disorders in pregnant women with gestosis. Journal of Obstetrics and Women's Diseases. – 2013; 62 (6): 5–12.
• Degtyarev D.N., Karpova A.L., Mebelova I.I. and others. Draft clinical recommendations for the diagnosis and treatment of hemorrhagic disease of newborns // Neonatology. 2015. No. 2. P. 75–86.

Hemophilia

Which doctors should I contact?

A hematologist treats patients with hemophilia. To confirm the presence of hemorrhagic manifestations or their consequences, consultation with specialists is also recommended. According to indications, consultations are possible:

• neonatologist or;
• geneticist;
• traumatologist-orthopedist;
• ;
• ;
• ;
• ;
• dentist

Treatment of hemophilia
Hemophilia is an incurable disease, so the main goal of therapy is to relieve symptoms. The main principle of treatment is specific replacement therapy with coagulation factor concentrates. Factor concentrates are made either from human plasma (plasma) or they are genetically modified (recombinant).

When products are made from plasma, a number of measures are taken to ensure that the product is free of viral infection and that patients will not become infected with viruses such as hepatitis C or HIV. To this end, strict criteria are applied to the selection of plasma donors. In addition, manufacturers have developed various methods to purify and inactivate viruses during the blood product manufacturing process. However, patients should be aware that there is a theoretical possibility of infection through the use of plasma products.

Recombinant drugs are created from living cells, such as monoclonal antibodies. They are considered technologically more advanced and carry a lower risk of viral infection.

Currently, there is no basis for a preferential choice between plasma-derived or recombinant drugs. Coagulation factor concentrates are administered intravenously. However, in about 30% of patients with severe hemophilia, the body begins to produce antibodies, which makes treatment extremely difficult, and in some cases impossible.

There are two types of specific therapy - preventive and treatment upon the occurrence of bleeding (on demand). In all cases, it is recommended to immediately use a sufficient dose and observe the frequency of administration of the drug.

For the treatment of hemophilia, newer drugs include fitusiran (reduces the production of the natural anticoagulant protein, antithrombin) and concizumab (increases the production of thrombin). Gene therapy using an adenoviral vector to deliver the factor VIII or IX gene is also being tested in clinical trials.

Complications

Serious complications occur with severe and moderate hemophilia and most often manifest themselves in the form of joint destruction and the development of arthritis. Bleeding into the joint leads to the destruction of its normal tissues and the development of chronic arthritis, which is very painful and leads to dysfunction of the joint. Hemorrhages in the joints are also observed in children from 2-3 years of age. Most often, large joints are affected - knees, elbows, ankles. If bleeding continues, the risk of disability and limitation of movement in the joint is extremely high (in the worst case, a person may lose a limb).

In addition to the negative impact on a person’s quality of life, hemorrhages often become life-threatening if they occur in vital organs, such as the brain.

Prevention of hemophilia

Preventive replacement therapy with blood coagulation factor concentrates is a necessary condition for maintaining the physical and psychological health of patients with severe and moderate hemophilia. Prophylactic treatment is usually given to children to reduce the risk of bleeding and joint damage. Recently, prevention has been prescribed to older people for the same purpose. Prevention involves infusion of clotting factor on a regular basis (every other day) to maintain normal blood clotting in the patient and prevent spontaneous bleeding.

Children with hemophilia must be protected from injury and tooth extraction prevented through careful oral hygiene and qualified dental care.

Before surgery or tooth extraction, patients undergo factor replacement therapy (preferably using a recombinant drug).

Young people should realize that maintaining physical activity is very important to strengthen muscles, ligaments and joints. Muscle weakness and poor coordination significantly increase the likelihood of joint injury and subsequent development of inflammation (arthritis). Good physical shape and a strong muscle frame reduce the risk of sporadic bleeding. The optimal sport for people with hemophilia is swimming.

People with hemophilia are encouraged to wear a medallion with information about the disease. This can save lives in a critical situation.

To prevent bleeding, hemophiliacs should avoid aspirin and nonsteroidal anti-inflammatory drugs because they slow platelet function.

Vaccinations do not pose a great danger to a person with hemophilia. Moreover, the list of mandatory ones includes a vaccine against hepatitis B. Most medications should still be taken orally due to the risk of bleeding when administered intramuscularly.

Sources:

1. Clinical guidelines for the diagnosis and treatment of hemophilia. National Society of Hematology. Under the leadership of academician V.G. Savchenko // – Moscow. – 2022. – 34 p.
2. Rumyantsev A.G., Rumyantsev S.A., Chernov V.M.. Hemophilia in the practice of doctors of various specialties // - Moscow. – 2012. – 132 p.
3. .
4. .

IMPORTANT!

The information in this section cannot be used for self-diagnosis and self-treatment. In case of pain or other exacerbation of the disease, diagnostic tests should be prescribed only by the attending physician. To make a diagnosis and properly prescribe treatment, you should contact your doctor.