Thrombocytopenia is a quantitative violation of the platelet link of hemostasis, characterized by a decrease in the number of platelets per unit volume of blood. Clinical signs of thrombocytopenia include increased bleeding from damaged skin and mucous membranes, a tendency to bruise and hemorrhagic rash, spontaneous bleeding of various localizations (nasal, gingival, gastric, uterine, etc.). Hematological diagnosis is based on the study of a blood test with platelet count, immunological examination, bone marrow punctate examination. Possible methods of treatment are drug therapy, splenectomy, extracorporeal blood purification.
Meaning
Thrombocytopenia – bleeding diathesis of various etiology, pathogenesis and course, characterized by a tendency to increased bleeding due to a decrease in the number of blood plates. The threshold criterion for thrombocytopenia in hematology is considered to be the platelet level below 150×109/l. However, the detailed clinical picture usually develops with a decrease in platelets to 50×109 / l, and the level of 30×109 / l and below is critical. Physiological thrombocytopenia that occurs in women during menstruation or pregnancy (gestational form) usually does not reach a pronounced degree. Pathological thrombocytopenia due to various causes occur in 50-100 people out of 1 million.
Platelets (Bicocero plaques) are small blood plates 1-4 microns in size. They are formed from megakaryocytes of the bone marrow under the direct stimulating effect of the polypeptide hormone thrombopoietin. The normal platelet level is 150-400×109/l; approximately 70% of platelets continuously circulate in the peripheral blood, and 1/3 of them are in the splenic depot. The average life expectancy of platelets is 7-10 days, after which their destruction occurs in the spleen.
Causes
Congenital thrombocytopenia is mostly part of hereditary syndromes, such as Viscot-Aldrich syndrome, Fanconi anemia, Bernard-Soulier syndrome, Mey-Hegglin anomaly, etc. Since hereditary thrombocytopenia, as a rule, qualitative changes in platelets are also observed, they are usually referred to as thrombocytopathies.
The causes of acquired thrombocytopenia are extremely diverse. Thus, the compensation of blood loss by infusion media, plasma, erythrocyte mass can lead to a decrease in platelet concentration by 20-25% and the occurrence of so-called dilution thrombocytopenia. Pathology of distribution is based on the sequestration of platelets in the spleen or vascular tumors – hemangiomas with the shutdown of a significant amount of platelet mass from the general blood flow. Disease distribution can develop in diseases accompanied by massive splenomegaly: lymphomas, sarcoidosis, portal hypertension, spleen tuberculosis, alcoholism, Gaucher’s disease, Felty syndrome, etc.
The most numerous group consists of thrombocytopenia caused by increased destruction of platelets. They can develop both in connection with the mechanical destruction of platelets (for example, with prosthetics of heart valves, artificial circulation, paroxysmal nocturnal hemoglobinuria), and in the presence of an immune component.
Alloimmune thrombocytopenia may be a consequence of transfusion of non–group blood; transimmune – penetration of maternal antibodies to platelets through the placenta to the fetus. Autoimmune form is associated with the production of antibodies to their own unchanged platelet antigens, which occurs in idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autoimmune thyroiditis, myeloma, chronic hepatitis, HIV infection, etc.
Heteroimmune thrombocytopenia is caused by the formation of antibodies against foreign antigens fixed on the surface of platelets (medicinal, viral, etc.). Drug-induced pathology occurs when taking sedative, antibacterial, sulfonamide drugs, alkaloids, gold compounds, bismuth, heparin injections, etc. A reversible moderate decrease in the number of platelets is observed after viral infections (adenovirus infection, influenza, chickenpox, rubella, measles, infectious mononucleosis), vaccination.
Thrombocytopenia caused by insufficient platelet formation (productive) develops with a deficiency of hematopoietic stem cells. This condition is characteristic of aplastic anemia, acute leukemia, myelofibrosis and myelosclerosis, tumor metastases to the bone marrow, iron deficiency, folic acid and vitamin B12, the effects of radiation therapy and cytostatic chemotherapy.
Finally, consumption thrombocytopenia occurs due to the increased need for platelets to ensure blood clotting, for example, in DIC syndrome, thrombosis, etc.
Classification
Thrombocytopenia is usually classified on the basis of a number of signs: causes, nature of the syndrome, pathogenetic factor, severity of hemorrhagic manifestations. According to the etiological criterion, primary (idiopathic) and secondary (acquired) thrombocytopenia are distinguished. In the first case, the syndrome is an independent disease; in the second, it develops a second time, with a number of other pathological processes.
Thrombocytopenia can have an acute course (lasting up to 6 months, with a sudden onset and a rapid decrease in the number of platelets) and chronic (lasting more than 6 months, with a gradual increase in manifestations and a decrease in platelet levels).
Taking into account the leading pathogenetic factor, there are:
- dilution thrombocytopenia
- thrombocytopenia distribution
- consumption thrombocytopenia
- thrombocytopenia caused by insufficient platelet formation
- thrombocytopenia caused by increased destruction of platelets: nonimmune and immune (alloimmune, autoimmune, transimmune, heteroimmune)
The criterion for the severity of thrombocytopenia is the level of blood platelets and the degree of hemostasis disorder:
- I – the number of platelets 150-50×109 / l – hemostasis satisfactory
- II – the number of platelets 50-20 x109 / l – with a minor injury, intradermal hemorrhages, petechiae, prolonged bleeding from wounds
- III – the number of platelets 20×109 / l and below – spontaneous internal bleeding develops.
Thrombocytopenia symptoms
Usually, the first signal of a decrease in platelet levels is the appearance of skin hemorrhages with minor injury (impact, compression) of soft tissues. Patients note the frequent occurrence of bruises, specific small-point rash (petechiae) on the body and limbs, hemorrhages in the mucous membranes, increased bleeding of the gums, etc. During this period, thrombocytopenia is detected only on the basis of changes in the hemogram, more often examined for another reason.
At the next stage, there is an increase in bleeding time with minor cuts, prolonged and abundant menstrual bleeding in women (menorrhagia), the appearance of ecchymosis at injection sites. Bleeding caused by trauma or medical manipulation (for example, tooth extraction) can last from several hours to several days. Splenomegaly in thrombocytopenia usually develops only against the background of concomitant pathology (autoimmune hemolytic anemia, chronic hepatitis, lymphocytic leukemia, etc.); liver enlargement is not characteristic. In the case of arthralgia, one should think about the presence of collagenosis in the patient and the secondary nature of thrombocytopenia; with a tendency to form deep visceral hematomas or hemarthrosis, about hemophilia.
With a significant decrease in the number of platelets, spontaneous bleeding occurs (nasal, uterine, pulmonary, renal, gastrointestinal), pronounced hemorrhagic syndrome after surgical interventions. Profuse uncupable bleeding and brain hemorrhages can become fatal.
Diagnostics
In any conditions accompanied by increased bleeding, you should consult a hematologist. The first test on the way to diagnose thrombocytopenia is a study of a general blood test with a count of the number of platelets. A peripheral blood smear may indicate a possible cause of thrombocytopenia: the presence of nucleated erythrocytes or immature leukocytes most likely indicates in favor of hemoblastosis and requires a more in-depth examination (sternal puncture, trepanobiopsy).
To exclude coagulopathy, a hemostasiogram is examined; if the autoimmune nature of thrombocytopenia is suspected, antiplatelet antibodies are determined. A possible cause of thrombocytopenia can be detected by ultrasound of the spleen, chest X-ray, enzyme immunoassay. Differential diagnosis is carried out between various forms of thrombocytopenia, as well as with Willebrand’s disease, hemophilia, pernicious anemia, thrombocytopathies, etc.
Thrombocytopenia treatment
When establishing the secondary nature of thrombocytopenia, the main treatment consists in the therapy of the underlying disease. At the same time, the presence of a pronounced hemorrhagic syndrome requires hospitalization of the patient and emergency medical care. With active bleeding, platelet transfusions, the appointment of angioprotectors (etamzilaa), fibrinolysis inhibitors (aminocaproic acid) are indicated. The intake of acetylsalicylic acid, anticoagulants, NSAIDs is excluded.
Patients with idiopathic thrombocytopenic purpura undergo glucocorticoid therapy, intravenous administration of immunoglobulin, plasmapheresis, cytostatic chemotherapy. In some cases (with the ineffectiveness of drug therapy, repeated bleeding) splenectomy is indicated. In case of non-immune thrombocytopenia, symptomatic hemostatic therapy is performed.
Literature
- Renal replacement therapy and concurrent fluconazole therapy increase linezolid-related thrombocytopenia among adult patients. Hsu YC, Chen SY, Hung YJ, Huang YW. Sci Rep. 2022 Jun 14;12(1):9894. link
- Elucidation of a Causal Relationship Between Platelet Count and Hypertension: A Bi-Directional Mendelian Randomization Study. Chiu PC, Chattopadhyay A, Wu MC, Hsiao TH, Lin CH, Lu TP. Front Cardiovasc Med. 2021 Nov 26;8:743075. link
- Platelet variability index: a measure of platelet count fluctuations in patients with immune thrombocytopenia. Li N, Heddle NM, Nazy I, Kelton JG, Arnold DM. Blood Adv. 2021 Oct 26;5(20):4256-4264. link
- Meropenem-induced thrombocytopenia: a paediatric case. Cachia J, Torpiano P, Pace D. BMJ Case Rep. 2021 Sep 3;14(9):e243443. link