The structure and function of platelets
Platelets are small blood cells. They play an important role in stopping bleeding and starting the repair of injured blood vessels.
Stages of blood coagulation
When a vessel is damaged, there are four stages of clot formation:
- Stage 1: the blood vessel ruptures and bleeding begins.
- Stage 2: the vessel contracts to slow the flow of blood into the damaged area.
- Stage 3: platelets stick to the walls of damaged blood vessels and coat them. This is called platelet adhesion. Platelets that spread through the vessels release substances that activate other nearby platelets, which accumulate at the site of damage to form a platelet plug. This is called platelet aggregation.
- Stage 4: adhesion proteins circulating in the blood are activated on the surface of platelets, forming a fibrin clot.
Proteins operate in a chain reaction. This is called the coagulation cascade.
Platelet components
Platelets have several important components to keep them functioning properly.
Receptors
These are proteins on the surface of platelets that allow the cell to interact with the vessel wall or another blood cell. There are two receptors that are very important for platelet adhesion and aggregation: glycoprotein Ib / IX / V and glycoprotein IIb / IIIa. The first of them provides adhesion and distribution of platelets at the site of damage to the vessel, and the second is necessary for platelet aggregation and the formation of a plug.
Granules
These are small containers, the contents of which are released when the platelets are activated. There are two types of pellets:
- alpha granules contain proteins that help platelets to adhere to other cells and promote vascular healing;
- beta granules contain substances that promote platelet activation and constriction of the blood vessel.
Thrombocytopathy - This is a clinical syndrome characterized by increased bleeding due to qualitative inferiority of platelets at their normal level in the blood.
Platelet dysfunctions can affect blood clotting in several ways, depending on the type of disorder:
- cells do not adhere to the walls of the vessel at the site of injury;
- platelets do not clump together to form a plug;
- cells do not activate blood proteins to form a solid fibrin clot.
Causes
Internal
They are as follows:
- mutation of a gene responsible for the work of factors involved in the process of blood coagulation;
- blood disease, accompanied by thrombocytopenia (leukemia, lymphogranulomatosis, reticulosis);
- chronic hemorrhagic anemia;
- allergy to foods containing protein;
- liver disease;
- diffuse connective tissue diseases.
Exogenous
They are as follows:
- the use of many drugs (anticoagulants and non-steroidal anti-inflammatory drugs - NSAIDs);
- acute and chronic infections (measles, whooping cough, tuberculosis, malaria).
Classification of thrombocytopathies
Congenital
Congenital platelet dysfunction is hereditary. They are passed from parent to child at conception.
In some families, the disorder is transmitted in an autosomal dominant manner, i.e. when it is enough for one parent to carry the mutated gene for the manifestation of the disease.
Another type of inheritance of platelet dysfunction, autosomal recessive, suggests that both parents must carry the defective gene and pass it on to their children for the disease to manifest.
Bernard-Soulier Syndrome (SBS)
SBS is a congenital platelet dysfunction when platelet adhesion is impaired. Patients with SBS have high platelet counts, but they do not function properly. The disorder is caused by a deficiency of glycoprotein Ib / IX / V. A lack of this protein will lead to prolonged bleeding because platelets do not clot.
SBS is usually an inherited disorder. Although there have been cases of acquired SBS in the medical literature, most of them have been associated with other conditions.
In the case of SBS, one of the genes located on a particular chromosome has a defect.
The abnormal gene is located on a chromosome that does not determine the sex of the child. This means that SBS can affect men and women, unlike other bleeding disorders such as factor VIII deficiency (also called hemophilia A), where severe cases are seen only in men because the defective gene is sex-related.
SBS is inherited in an autosomal recessive manner. A person who inherits the defective gene from only one of their parents is a carrier who is unlikely to show any symptoms of the disease.
Glanzman's thrombastenia
A rare hereditary blood clotting disorder. It affects platelet aggregation (the ability to accumulate around a damaged blood vessel). With this pathology, platelets are present in normal quantities, but they cannot work normally. Glanzmann's thrombastenia is caused by a deficiency of glycoprotein IIb / IIIa. Due to its lack, platelets do not form a plug to stop bleeding
The disorder is inherited in an autosomal recessive manner and can affect people of both sexes.
Disorders of platelet function associated with their secretion
The functions of platelets are impaired due to a violation of the mechanisms of their formation:
- Gray platelet syndrome - a rare hereditary blood clotting disorder in which platelets are gray. The disease is the result of the absence or reduction of alpha granules in platelets.
- Beta Granule Deficiency characterized by a lack of granules in which certain substances are stored, which are necessary for normal platelet activation.
- Secretory mechanism disorders involve the inability of normal granu to release their contents when platelets are activated.
Disorders of procoagulant activity
With these disorders, the platelet cannot activate blood clotting factors. In this case, platelet aggregation remains normal, but abnormalities are possible on the phospholipid surface of the cell, where some coagulation factors are formed.
Acquired thrombocytopathies
Secondary thrombocytopathies in systemic diseases
- Uremia (violation of the filtering function of the kidneys). Thrombocytopathy is caused by toxic decay products. After dialysis (artificial blood purification), platelet function and bleeding time return to normal.
- Cirrhosis of the liver. Multiple bleeding is determined by coagulation disorders, increased fibrinolysis (the process of dissolution of blood clots) and thrombocytopenia. Platelet function is also usually impaired.
- Myeloproliferative pathologies (excessive production of blood components). Essential thrombocythemia, primary polycythemia, chronic myeloid leukemia may be associated with thrombocytopathy.
- Other diseases. Autoimmune disorders, severe burns, and cardiac abnormalities can affect platelet function. Various disorders of hemostasis (blood coagulation system), including thrombocytopathy, during heart surgery are determined by the use of a heart-lung machine.
Pharmaceutical Thrombocytopathy
Many drugs affect the functioning of platelets, but most of them in therapeutic doses have no clinical significance.
- Acetylsalicylic acid inhibits (inhibits) the action of platelets by irreversibly affecting cyclooxygenase (platelet enzyme). As a result, the production of thromboxane A (an aggregation stimulator) is blocked. Inhibition continues throughout the life of the cell;
- NSAIDs also inhibit the chain of reactions leading to the synthesis of thromboxane, but inhibition is reversible and lasts as long as the drug is in the body.
The main manifestations of thrombocytopathies in children
Clinical manifestations are polymorphic and depend on the forms of thrombocytopathy, but most hereditary platelet dysfunctions are manifested by the following symptoms:
- manifest at an early age;
- bleeding increases with infections, taking medications;
- post-traumatic hemorrhages (hemorrhages) are dangerous, in addition, slow wound healing is observed.
Acquired thrombocytopathies usually have a clear connection with one or another pathological condition or medication that disrupts platelet aggregation.
Features of hemorrhagic syndrome
Hemorrhagic syndrome is a disease of the hematopoietic system, its main manifestations:
- increased bleeding;
- tendency to repeated bleeding and hemorrhage, spontaneous or after minor trauma.
Distinctive features of thrombocytopathy:
- hemorrhages in the skin, mucous membranes;
- profuse bleeding, inappropriate to the degree of injury;
- hemorrhagic skin rash (a combination of petechiae (pinpoint spots) and bruising), the elements of which are located asymmetrically.
Hemorrhagic rashes are localized on the legs and lower half of the body, mainly on the front surface of the abdomen. Especially often, the rash first appears in areas of squeezing and rubbing of the skin with clothing.
Petechiae and ecchymosis (bruises) quickly appear after minimal damage to microvessels: due to friction of clothing, minor bruises, injections. Sometimes there are recurrent bleeding from the nose and gastrointestinal tract, hematuria (blood in the urine).
The most severe consequences include:
- hemorrhages in the inner lining of the eye with loss of vision;
- hemorrhages in the brain and its membranes.
Anemic syndrome
Repeated even minor blood loss greatly aggravates the child's condition. As a result, anemic syndrome may develop. It occurs when the number of circulating red blood cells (red blood cells) decreases in the body.
The most common symptoms of anemia are tiredness and lack of energy.
Other common symptoms may include:
- pallor of the skin;
- fast or irregular heartbeat;
- shortness of breath;
- chest pain;
- headache.
Combination of thrombocytopathies with congenital connective tissue disorders
When thrombocytopathy in children accompanies connective tissue dysplasia, the following can be detected:
- posture abnormalities;
- flat feet;
- increased mobility of the kidney (nephroptosis);
- dysfunction of the heart valve, etc.
What diagnostic methods can confirm the diagnosis of thrombocytopathy?
Thrombocytopathy is not easy to diagnose. Parents who suspect their child has a clotting problem should see a hematologist.
The symptoms of platelet dysfunction are similar to those of other blood clotting disorders. To accurately identify the problem will require a number of studies.
General blood analysis
The test is done to measure the number of platelets. This will determine if the child's symptoms are caused by a lack of platelets (thrombocytopenia).
Determination of the time interval of bleeding
The bleeding time is measured in the following way: a cuff is put on the shoulder and the pressure is pumped up to 40 mm, and a small incision is made on the forearm. The time taken to stop bleeding is measured using a stopwatch. The time interval for bleeding is longer than usual in patients with reduced platelet count or platelet dysfunction.
Study of platelet aggregation function
Platelets are removed from a blood sample and placed in a special device, an aggregometer, where platelet thickening is monitored. Special substances are added to stimulate aggregation.
If aggregation does not occur or it is reduced, this indicates the presence of abnormalities in the platelet granules.
Treatment
Approaches to the therapy of hereditary thrombocytopathies
Congenital thrombocytopathies are associated with a wide range of symptoms. However, as a rule, there is no specific therapy for the vast majority of patients, and only severe cases need to be treated.
Treatment for congenital platelet dysfunctions includes:
- preventing bleeding;
- the use of supportive therapy to control hemorrhagic syndrome.
But because the type and severity of bleeding varies from patient to patient, therapeutic approaches must be personalized.
Medicines
Desmopressin is a drug that can be used to shorten bleeding time and reduce blood loss in many patients with thrombocytopathy. It can be administered intravenously or subcutaneously, before surgery or after an injury, to prevent or reduce excessive bleeding.
Recombinant factor VIIa may be effective for bleeding in some patients with Glanzmann thrombasthenia or Bernard-Soulier syndrome and for preventing bleeding before surgery. Can be used as an alternative to platelet transfusions to prevent patients from developing antibodies to platelets or to continue treatment when antibodies have already developed.
Platelet transfusion
This method is used for severe uncontrolled bleeding or to prevent bleeding during or after surgery. Although platelet transfusions can be very effective, they should be avoided whenever possible because some children may develop antibodies to platelets. As a result, subsequent transfusions will not be beneficial.
Treatment of acquired thrombocytopathies
Treatment for acquired platelet dysfunctions depends on the primary factor causing the disorder:
- treatment of the underlying disease responsible for the condition usually helps to eliminate the pathology;
- if bleeding occurs due to taking the medication, then it should be canceled.
- when renal failure becomes the cause of thrombocytopathy, dialysis, blood transfusion are performed, from drugs Erythropoietin, Desmopressin are used;
- platelet transfusions are performed when the above treatment options fail to stop the bleeding, regardless of the cause.
With acquired thrombocytopathies, adequate therapy of the underlying disease is required against the background of symptomatic hemostatic therapy.
Forecast
The prognosis is favorable with dynamic observation and the implementation of the recommendations of the hematologist.
Clinical examination of children
Children with platelet dysfunction should undergo regular medical examinations, regardless of the existence of a hemorrhagic episode. A pediatrician and hematologist should examine the child at least once every 6 months, an otolaryngologist and dentist - at least once a year. In addition, laboratory monitoring should be carried out - a general blood test, urine, coagulogram, a study of platelet aggregation, at least once every six months.
Prevention
Preventive measures include:
- observance of the general rules of behavior, excluding the receipt of mechanical injuries;
- limiting the consumption of products containing salicylates;
- exclusion of taking medications with antiplatelet and anticoagulant effect.
Conclusion
Platelets are essential for primary hemostasis. Thrombocytopathies include a large and heterogeneous group of blood clotting disorders that range in severity from mild to severe.
Patients may be asymptomatic, but most will have mild bruising and bleeding, or excessive bleeding after injury or surgery.
According to the type and severity of the disease, the doctor will offer some recommendations for controlling the condition. It is also recommended that other family members get tested for platelet dysfunction.
