Thrombocytopenic purpura. Haemophilia. Thrombocytopenic purpura Hemorrhagic diathesis

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1 Thrombocytopenic purpura. Haemophilia. Thrombocytopenic purpura (idiopathic thrombocytopenic purpura, Verlgofa disease) and hemophilia (A, B, C) belong to the group of hemorrhagic diseases and syndromes (hemorrhagic diathesis), a common feature of which is the manifestation of bleeding from the lungs "visual" form to fatal bleeding who require immediate action. Hemorrhagic diathesis - clinical conditions when diagnosed symptoms associated with the release of blood vessels: bleeding in the skin, mucous membranes, joints, tissues, profuse bleeding that is not the result of random (aggressive) traumatic surgery. Classification: Hemorrhagic diathesis: 1. Thrombocytopenia and Thrombocytopathy (amegakariocytic): A. Thrombocytopenia (TP) I. Reduced produced: Innate Acquired (hypo, aplasia of bone marrow, myelotoxic drug / chemical / viral infections, cancers, radiation effects) II. Enhanced degradation (megakariocytic): Immune (autho-, allo-, medication), formerly known as: idiopathic TC - disease Verlgofa; Microangiopathic (TTP - thrombotic thrombocytopenic purpura, hemolytic uremic syndrome, disseminated intravascular coagulation); Other (infection, massive transfusion). III. Redistributive: In splenomegaly In syndrome of "hypersplenism" IV. Psudotrombocytopenic: In hemodilution "platelet satelizm" B. Thrombocytopathy (normal platelet count but violated some of their functions) I. Innate: Lack of platelet receptors (to collagen, prostaglandin, and epinephrine) Violation of the adhesive properties of platelets (illness Vilebranda) Violation of platelet aggregation properties (lack or absence of gp IIb IIIa, congenital afibrynogenia) Violation of secretory properties of platelets (lack of COX-1, thromboxane synthetase) Violation of coagulation activity of platelets.

2 II. Acquired: Medication (aspirin other antiplatelet agents, NSAIDs, penicillins, cephalosporins, nitrates, calcium antagonists, antihistamines, thrombolytics) Hematologic diseases (myelo-, lymphoproliferative, paraproteinemic) Systemic diseases / syndromes (uremia, hepatic failure, DIC, etc.) 2. Coagulopathy I. Innate: Haemophilia A (f.viii deficiency), hemophilia B (deficiency of f.ix) Other deficient states (ff. II, B, VII, X, XI, XIII, fibrinogen) Von Willebrand disease Deficiency of alpha-2-antiplasmin II. Acquired: Vitamin K deficiency (malabsorption, prolonged antibiotic therapy, use of oral anticoagulants, prematurity) Anticoagulation therapy Severe hepatic insufficiency Heavy dysproteinemia (myeloma, cryoglobulinemia, other paraproteinemias) Antibodies to clotting factors. 3. Vasopathy I. Without the presence of inflammation of blood vessels: Congenital vascular disease (Osler-Rand, Fabry, Kazabaha-Merritt) Congenital connective tissue (Ehlers-Danlos syndrome disease, Marfan, etc.) Acquired (some innate) (homocistenuria, vitamin C deficiency, protein metabolism pathology, etc.) Idiopathic (syndrome Gardner -Dayamonda, Shamberha, simple purple, etc.) Medicamentous, chemical exposure, poison II. With the presence of an inflammatory component in vessels: Primary hemorrhagic vasculitis Secondary hemorrhagic vasculitis (infectious, allergic infectious, autoimmune, neoplastic, medication). A typical hemorrhagic vasculitis is Schonlein-Henoch disease attributable to immunocomplex diseases that arise when damaging impact on vessels of low immune complexes with the development of multiple micro thrombovasculitis. By clinical features distinguish skin shape (symmetric petechiae on the buttocks and legs), joints (synovitis), abdominal (bleeding in the gastrointestinal tract and peritoneum accompanied by severe abdominal pain), renal (like jade), fast leaking cerebral form (bleeding in the brain) and various combinations. 4. Hemorrhagic diathesis caused by the combined factors: angiohemophilia (von Willebrand disease). Algorithm of clinical diagnosis of hemorrhagic diathesis.

3 The basis of the algorithm diagnosis of hemorrhagic diathesis is recognition of the type of bleeding in the patient by analyzing the anamnesis and clinical examination. There are 5 main types of bleeding: I. Haematomic type. Characterized by massive, intense, deep and very painful hemorrhages in joints, muscles, subcutaneous and retroperitoneal fat, in the peritoneum, subserous membrane of the intestine and accompanied clinic of abdominal catastrophe (appendicitis, bowel obstruction, peritonitis, colic, etc.). At examination large joints are deformed, their contours are smoothed, and mobility is limited. Haematomic syndrome is often associated with profuse spontaneous, posttraumatic and postoperative bleeding, which can be later, a few hours after injury or surgery. II. Petechial-spotted type. Manifested by numerous points (petechiae) and spotted hemorrhages in the skin in the form of bruises and «smudges of blood» (ecchymosis). Petechiae and ecchymosis do not disappear when pressed, easily arise during skin microvascular injury in compression tight clothing ("impression") cuff when measuring blood pressure ("cuff"). Are frequent bleeding from the gums, gastrointestinal bleeding, and meno- metrorrhagia. III. Mixed bruises - haematomic type. Blood smudges common with sealing skin in places bruising, are painful. Prevalence of hematoma in the subcutaneous and retroperitoneal fat, in the mesentery, subserous intestinal membrane. IV. Vasculitis - purple type. Characterized by haemorrhages in the form of rash combined with elements of erythema. Hemorrhages arise against the background of exudative inflammatory changes; rise above the level of the skin, often surrounded by rim pigmentation, sometimes covered by crust. V. Angioma type. Accompanied by stubborn bleeding that often repeated with some localization (with vascular dysplasia). The most common is profuse nosebleeds. The main therapeutic options (rules) treatment of hemorrhagic diathesis, Thrombocytopenia, Thrombocytopathy: Against the backdrop of control of the underlying disease: Immuni: steroids, cytotoxic agents (vinkrystin, cyclophosphamide, imuran), immunoglobulins (Sandoglobulin, Intraglobin-F), cyclosporine, interferons, monoclonal antibodies, plasmapheresis. Splenectomy in most cases refractory thrombocytopenia useful, but needs carefully weighed evidence of diagnosis (splenectomy is not recommended for children under 6 years because of the possibility of sepsis). In life-threatening bleeding (primarily gastrointestinal or neurological) is shown i /v platelet concentrate 4-6 times a day + i / v immunoglobulin 1.0 / kg + in low efficiency mg of methylprednisolone. Possible urgent splenectomy. In pregnancy, cesarean section is shown only in the presence of obstetric and anatomical conditions. Newborn require laboratory monitoring of thrombocytopenia.

4 When invasive interventions is shown prophylactic infusion of thromboconcentrate, preferably with reaching x 10 * 9 / L platelets, in neurological or ophthalmological interventions - 100h10 * 9 / L. When diagnosed Thrombocytopathy steroids are ineffective, even harmful (!) In TTP, hemolytic uremic syndrome - thromboconcentrates are contraindicated (!!) Coagulopathy Medicines that are used: SZP- fresh frozen plasma, CP- cryoprecipitate, prothrombin complex, DDAVP- (deamino-deargynin-vasopressin / Desmopressin). In haemophilia A, B, treatment is divided by the urgent treatment and preventive (drugs are the same dose and regimen different) developed schemes / dose depending on the specific location of bleeding. Vasopathy Control of underlying disease in most cases sufficient effective Symptomatic treatment is aimed at the elimination of local bleeding (adrenaline EAKK, operation) In infectious vasopathy is effective antibiotic therapy. Cancel of medications that may have caused vasopathy. In most cases, treatment with vitamins C, P and etamzilat gives positive results. Immunosuppressant (including corticosteroids) should not be prescribed routinely. There must be evidence of immunocompetence vasopathy. Do not prescribe medications that affecting the platelet function or synthesis of coagulation factors. Idiopathic thrombocytopenic purpura Definition: Idiopathic thrombocytopenic purpura (ITP),(disease Verlgofa, autoimmune thrombocytopenia idiomatic) is primary thrombocytopenia with autoimmune mechanism of formation antiplatelet antibody. Pathogenesis: The destruction is caused by platelet phagocytosis by macrophages in the spleen, liver. The average life span of platelets in ITP often shortened to 15 hours, whereas in norm it is 220 hours. Classification: Are distinguished two forms of ITP: - Acute - with sudden onset in children from 2 to 6 years and a recovery period up to 6 months. - Chronic - with hidden beginning, rare spontaneous remissions and frequent relapses. The peak incidence - aged 20 to 40 years.

5 An example of formulation of diagnosis: Idiopathic thrombocytopenic purpura, chronic, phase relapse. Chronic posthemorrhagic iron deficiency anemia, mild severity, hypochromic, normoregenerative, normoblastic. Clinical and laboratory data: The chronic forms of ITP suffer mostly women (3: 1). Hemorrhages in the skin in the form of petechiae and ecchymosis combined with nosebleeds, menorrhagia. Haematuria, melena, bloody vomiting are uncharacteristic. In 10-20% of patients observed moderate splenomegaly (usually by ultrasound). In peripheral blood - chronic posthaemorrhagic anemia of varying degree. In the bone marrow hyperplasia megacariocytic and erythrocyte germs. Diagnostic criteria: Haemorrhagic syndrome with petechial - ecchymosis type of bleeding. Lack of communication of bleeding from any background or previous disease. "Contact" haemorrhages in the skin (wearing tight clothing, belts, after deep palpation, etc.). Positive "vascular" samples (tow emergency, cuff, etc.). Thrombocytopenia in peripheral blood (below / l - to single platelets in the sample). Extension of capillary bleeding time (Duke test) at normal time parameters coagulation after Li-White. Violation of blood clot retraction (reduction index less than 40%) Identification of antiplatelet antibodies (Diksena method, according to IFA) and increase the level of circulating immune complexes (CIC), immunoglobulin G. The combination of autoimmune thrombocytopenia haemolytic with anaemia (positive direct Coombs test) - Fisher-Evans syndrome. Differential diagnosis: Aplastic anemia Immune thrombocytopenia is differentiated from secondary autoimmune TP on the background of systemic connective tissue diseases, autoimmune thyroid disease, redistributive heteroimmune TP against the background of splenomegaly and hypersplenism. Treatment: Use glucocorticosteroid hormones (average starting dose 60 mg / day). With the lack of effectiveness of corticosteroids administered delagil to 2 months under the supervision of leukocytes and consulting ophthalmologist. Also are used Immunosuppressants (azathioprine), immunomodulators (timalin, T-activin, splenin). With the ineffectiveness of conservative treatment in terms of 4 to 6 months of treatment - recommend splenectomy. The third direction of therapy at ITP is high dose (400 mg / kg) of immunoglobulin for intravenous administration for 5 days.

6 In critical conditions (acute haemorrhagic syndrome in reducing platelet below 20*109 / l) is performed transfusion of thromboconcentrate. With hemostatic purpose also appoint the frozen plasma, epsilon-aminocaproic acid, protease inhibitors, dycynon. At nasal bleeding carried out loose tamponade of nose with the use of hemostatic sponge and adrokson. Prevention: All patients should be under the medical observation of haematologist. Course, complications, and prognosis: Leaking chronic, relapsing and acute with complete recovery during 6 months (in children). The most serious complication observed with a decrease of platelets to 20-10*109 / l. Prognosis defined by character response to the therapy and course of the disease. Haemophilia Definition: diseases of the group coagulopathy caused by hereditary coagulation disorders of hemostasis, occurring with decreasing blood coagulation. Among coagulopathy of hereditary origins most common is deficiency of factors VIII (hemophilia A) and IX (hemophilia B). In some populations (Jews) is deficiency of factor XI (hemophilia C). Less commonly observed hereditary deficiency of factor VII (hipoproconvertinemia). Etiology and pathogenesis: Hemophilia A and B caused by a hereditary deficiency or molecular abnormalities VIII i IX coagulation factors, are transmitted by recessive type. Gene of hemophilia localized on the X chromosome, in connection with what women are conductors of the disease. With all common forms of hereditary coagulation factor deficiencies is a violation of the first phase of an isolated internal mechanism of blood coagulation. At deficiency of factor VII - violated external mechanism of protrombinasic activity. Classification: 1. By the prevalence allocate: Forms that often occur ( 1, 2, 3 in Table. 1), which make up 96-98% of cases of hereditary coagulopathy; Forms that occur rarely (4, 6, 7) - 2-3% of cases; Forms that occur very rarely (all others: 5, 8, 9, 10). 2. By the level of deficit of factor: Very heavy - 0-1%; Heavy - 1.2%; moderate - 2.5%; Easy - more than 5%.

7 Tab. 1. Classification of hereditary coagulopathy with reduced of blood coagulation. ICD - X scarce factor Name of disease пп D66,0 1. VIII K (antihemophilic Haemophilia A factor-globulin) D68,0 2. VIII FW (von Willebrand Von Willebrand disease factor) D67 3. IX (plasma thromboplastin Haemophilia B (Christmas component PTA) disease) D XI (plasma thromboplastin Haemophilia C (disease predecessor PTA) (Rosenthal) 5. XII (Hageman factor) defect Hageman 6. VII 9 (prokonvertin) Hipoproconvertinemia V (proakcelerin) Hipoproakcelerinemia 7. (parahaemophilia) D X (factor Stuart -Prauera) Disease Stewart-Prauera 9. I (fibrinogen) A (hypo) fibrinogenemia 10. XIII (fibrin stabilizing factor) Deficiency of fibrinstabilising factor (PSF). Example of formulation of diagnosis: Haemophilia A, severe form, acute haemarthrosis of the left knee. Haemophilic arthropathy of the right knee. Acute post haemorrhagic anemia moderate severity. The clinical picture: Clinical manifestations of hemophilia A and B are the same. Severe forms are diagnosed at birth, significant cephalhematoma, subcutaneous bleeding, and late bleeding from the umbilical ring. In mild and moderate forms disease is recognized at 2-3 years of age: random cuts, injuries, bite the tongue accompanied by copious bleeding. Later in the clinic is a dominated manifestation of haemophilic arthropathy. Acute haemarthrosis occur: severe forms at 2-3 years of age, with an average severity - from 4-6 years. Most often are affected knee, elbow ankle and foot, at least - shoulder, radio-carpal, hipbone joints. In 14-30% of patients have bleeding. The source profuse intestinal - gastric bleeding may be gastric ulcer and duodenum, use of nonsteroidal anti-inflammatory drugs, diffuse bleeding intestinal mucosa. Diagnostic criteria: Family history (in 1/3 patients indications of haemorrhagic disease in relatives may be absent - haemophilia is caused by gene mutations) Hematomic (I) type of bleeding. Haemophilic arthropathy: a combination of acute haemarthrosis (primary and recurrent) with chronic destructive osteoarthritis.

8 Early detection of soft tissue changes (hyperplasia and thickening), accumulation of blood in the articular bag and her pockets, haemosiderosis of synovial membrane, etc. by X - ray diagnostic methods (ultrasound, MRI - scan). Haematuria combined with attacks of renal colic (clots in the urinary tract % of patients. Continuation of time coagulation for Lee - White with normal figures for Duke bleeding time, platelet count, prothrombin time (hemophilia A and B). Secondary rheumatoid syndrome - symmetrical lesions of both large and small joints (including those not amazed hemorrhages): morning stiffness, pain; aggravation after replacement therapy; increase in plasma levels of rheumatoid factor, CRP, sialic acid, gamma globulin, etc.; radiological signs of rheumatoid arthritis (joint space narrowing, usury of the articular surfaces, etc.). Complications: Complications at haemophilia are associated with compression of bodies (stenosis of the larynx, trachea, etc.). It is also possible the development of sepsis, chronic posthaemorrhagic anemia. Differential diagnosis: Haemophilia A and B is differentiated with von Willebrand's disease and acquired coagulopathy. Treatment: The main method of treatment of bleeding in patients with haemophilia is replacement therapy within the first hour after bruises, injuries. At haemophilia A are effective: antihaemophilic plasma, cryoprecipitate, a concentrate f.viii, recombinant or purified monoclonal factor VIII. Also used drugs include a mixture of all synthesized in the liver K - vitamin dependent factors: IX, X, VII, II. The most famous PPSB (France), PPSB (Russia) (prothrombin + prokonvertin + factor Stewart (f.x) + antihemophilic globulin (f. IX). Tab. 2. The doses of coagulation factors needed for the introduction haemophilia patients in different clinical situations (S. Stabler, 1997) The clinical situation F VIII F ХІ Haemorrhage in soft tissue, moderate haemarthrosis, removal and stopping teeth Severe bleeding in the soft tissue or joint, surgery of the mouth, lumbar, pleural puncture Bleeding at large injuries profuse, gastro 20 U / kg (every 12 hours) 40 U / kg (1 time in 24 hours) 40 U / kg (every 12 hours) 80 U / kg (every 24 hours) U / kg (40 U / kg then 20 U / kg every U / kg (80 U / kg then 40 U / kg every 24

9 - intestinal bleeding, tonsillectomy, abdominal surgery Haemorrhage in the CNS Laceration that requires suture. hours 40 U / kg, then 20 u \ kg every 12 hours to resorption of hematomas (10-14 days) 40 од/кг під час накладання швів, потім через день до їх взяття hours) 80 U / kg every 24 hours until resolution of the hematoma (10-14 days) 40 U / kg during suture, then every other day for their removal The duration of treatment depends on the severity of bleeding. In mild bleeding into a joint or soft tissue to stop bleeding is enough 1-2 doses. At extensive bleeding in joints and soft tissue treatment should continue until the resolution of the haematoma. External bleeding besides replacement therapy stop by local impact: processing thromboplastin, hemostatic sponge, epsilon-aminocaproic acid. After the early aspiration of blood from the joint to relieve inflammatory changes recommended the introduction of mg hydrocortisone. Prevention: Patients with haemophilia should be on dispensary registration in haematologist and to have documents indicating the type of haemophilia, blood group, treatment that was conducted earlier. At any trauma, pain needs an urgent first aid, rest, limb immobilization in physiological position, warming it. Any internal muscle injections are contraindicated in patients with haemophilia.