Pathology of hPathology of hааemostasisemostasis

D.D., ProfessorDenefil Olha Volodymyrivna

Meaning

• 1. Control of blood fluid condition (is due to adequate correlation between activity of coagulative blood system and anticoagulative one)

• 2. Bleeding stop (is very important for control of the blood circulation index)

HAEMOSTASIS SYSTEMS COMPONENTS

• * VESSEL’S WALL

• * ТROMBOCYTES

• * SYSTEMS OF THE BLOOD PLASMA:

• - COAGULATIVE

• - ANTICOAGULATIVE • - FIBRINOLYSIS• - KALLIKREIN-KININ

HAEMOSTASIS SYSTEM

• VESSEL-TROMBOCYTE’S

(PRIMARY HAEMOSTASIS)

- Bleeding stop in micro vessels

• COAGULATIVE (SECONDARY)

FIBRIN CLOTS FORMATION

НАEMOSTASIS VIOLATION CLASSIFICATION

• BY ETHIOLOGY - HEREDITARY

- ACQUIRED

• BY PATHOGENESIS - VESSEL-PLATELETS НАEMOSTASIS VIOLATION

- COAGULATIVE НАEMOSTASIS VIOLATION

• BY DIRECTION OF THE CHANGES

• - HYPOCOAGULATION

- HYPERCOAGULATION

HYPOCOAGULATION

• REDUCED PROPERTY OF THE BLOOD TO FORM OF THE BLOOD CLOTS which results in spontaneous bleeding or hemorrhage

• (very often after trivial trauma)

ETHIOLOGY

• 1. THROMBOCYTOPENIA • 2. THROMBOCYTOPATHY

• 3. VASOPATHY

• 4. CОАGULOPATHY

THROMBOCYTOPENIA

Pathological condition which is characterized by the decreased amount

of thrombocytes in the blood

(LESS THEN 150·109 /l)

HEREDITARY THROMBOCYTOPENIA

• As a rule, is accompanied with hereditary thrombocytes defect

ACQUIRED THROMBOCYTOPENIA

• REASONS• INJURY OF THE THROMBOCYTES - by immune complexes - mechanical trauma (at spleenmegaly, haemangioma)

• THROMBOCYTES MATURATION DEPRESSION

(aplastic anemia, red bone marrow injury by chemical poisons and radiation, tumors in bone marrow – metastasis or primary)

• ACCELERATED USING OF THE THROMBOCYTES

(thrombosis, DIC-syndrome)

• HETEROIMMUNE Arises most often in children

Reason – change of thrombocyte’s antigen structure (attachment of the viruses at measles, smallpox; attachment of the medicine’s origin haptens; vaccines)

Clinical course is benign (elimination of the reason conduces to absolute recovery)

IMMUNE THROMBOCYTOPENIA

• AUTOIMMUNE Arises most often in adult

Reason – no immune system tolerance to own thrombocyte’s antigens

Provoked agents: medicines, viruses, bacteria

IMMUNE THROMBOCYTOPENIA

AUTOIMMUNE THROMBOCYTOPENIA

VERLGOFF’S disease1. Ig G amount on the platelets surface increases in 10 time 2. main place of Ig G synthesis is spleen 3. treatment principles: - spleenectomy - corticosteroids - depression of immune response by medicines * Absolute recovery is not

THROMBOCYTOPATY

• НАEMOSTASIS VIOLATION AS THE RESULT OF QUOLITATIVE

THROMBOCYTE’S DEFECTS OR THROMBOCYTE’S DYSFUNCTION, WHICH IS CHRACTERISE BY VESSEL-TROMBOCYTE’S НАEMOSTASIS VIOLATION, APPERENCE OF HAEMORHAGIES IN TISSUES AND ORGANS

HEREDITARY THROMBOCYTOPATY

• WITHOUT VIOLATION OF GRANULES EXCRETION

GLANCMAN’S disease *Type of inheritance - autosomal-recessive *Reason - no glycoproteins 2в and 3а in

thrombocite’s membrane *Pathogenesis – thrombocytes cannot

interact with fibrinogen, so they don’t aggregate

*Signs: skin hemorrhages, nasal bleeding, uterine bleeding (some time deadly!!)

• BECAUSE EXCRETION OF GRANULESIS VIOLATIED

Type of inheritance - autosomal-recessiveReason – violation of cycleoxigenase

activity, low activity of contractive proteins

Pathogenesis – no thrombocyte’s aggregation at collagen contact, no granules excretion

Signs: skin hemorrhages, nasal bleeding, uterine bleeding (some time deadly!!)

HEREDITARY THROMBOCYTOPATY

• DEFICIT OF GRANULES AND THEIR CONTENT

• HERDJMANSKY-PUDLAK’S DISEASE (AR)• Reason– deficit of the dense granules

(АDP, аdrenalin, serotonin, Са2+)

• Pathogenesis – no thrombocytes aggregation after contact with collagen, no excretion of the granules substances

• Signs: skin hemorrhages, nasal bleeding, uterine

bleeding

HEREDITARY THROMBOCYTOPATY

• VIOLATION OF THROMBOCYTE’S ADGESION AND AGGREGATION

• Willebrand-Jurgens syndrome (Аr)• Reason – von Willebrand’s factor deficit• Pathogenesis – violation of thrombocytes adhesion

because activity of c.f.8 is reduced• Bernar-Sulie’s disease (АR)

• Reason – no glycoprotein's 1 in thrombocyte’s membrane

• Pathogenesis – is violated interaction between thrombocytes and f.Willebrand, f. 5, f. 11

• Signs – capillary bleeding (particularly during sex aging and delivery)

HEREDITARY THROMBOCYTOPATY

THROMBOCYTE’S FACTOR 3 DEFICIT

• BOUE-OWEN’S disease• Reason – f.3 deficit in thrombocytes

• Pathogenesis – no interaction between thrombocytes and coagulative plasma factors

• Signs: skin hemorrhages, nasal bleeding, uterine bleeding

HEREDITARY THROMBOCYTOPATY

• COMBINATION OF THROMBOCYTOPATIA and OTHER

HEREDITARY ANOMALIES• VISCOTT-ОLDREEG’S syndr.

- Reason – reduced amount in thrombocytes dense granules (АDФ, аdrenalin, serotonin, Са2+) and alpha- granules (beta-thrombglobulin, fibrinogene, fibronectin, growth factor)

- Pathogenesis – weak adhesion and aggregation of the thrombocytes, no granules excretion

- Signs: hemorrhage syndrome appears in childhood (deadly bleeding is possible)

HEREDITARY THROMBOCYTOPATY

ACQUIRED THROMBOCYTOPATY (ETIOLOGY)

• 1. Leucaemia – granules deficit inside thrombocytes because their maturation is accelerated (reduced adhesion and aggregation)

• 2. Ig М accumulation (causes injury of thrombocyte’s receptors and violation of thrombocytes and coagulative factors interaction (at immune diseases)

• 3. Vitamin В12 deficit (causes violation of granules excretion)

• 4. Medicines

Medicine’s THROMBOCYTOPATY

* Thromboxan А2 synthesis inhibitors

- antiinflamational steroid medicines

- antiinflamational nonsteroid medicines (aspirin inhibits thrombocytes aggregation, effect last 4-6 days)

* Stimulation of cAMP synthesis

-papaverin

-euphillin

-anabolic steroids

* Са-ions blockers

-verapamil

-corinphar

VASOPATHY

• Hemorrhage diathesis caused by functional and morphological defect of vessel’s wall

HEREDITARY ACQUIRED

HEREDITARY VASOPATHY

• RANDIU-ОSLER’S dis., FABRE’S dis. • Reason – violation of connective tisue

development in vessel’s subendothelium - local thickening of the vessels - microvessel’s dilation - little of collagen fibers in subendothelium - vessels are very easy traumatized - weak adhesion end aggregation of the

thrombocytes as a result of collagen fibers deficit

Signs: – nasal bleeding, pulmonary-bronchial

bleeding, gastro-intestinal bleeding (some time deadly)

1. Idiopathial (Caposhi’s sarcoma) - ethiology – unknown2. Stagnantal (Klotc’s dermatitis, Fawr-Rakusho’s

dermatitis) - ethiology – chronic heart failure, local venous

insufficiency3. Distrophial - uprarenal glands hyperfunction, glucocorticoid

therapy (steroid purpura - occurs because collagen fibres synthesis depression)

- vitamin C deficit - vessel’s damage by immune complexex (Shenliayn-Ganouh’s diseas)

Signs: – skin haemorrhagies

ACQUIRED VASOPATHY

CОАGULOPATHY

• Pathological state which results from deficit of coagulative system activity

HEREDITARY ACQUIRED

HEREDITARY CОАGULOPATHY

• Group of the diseases caused by hereditary deficit or hereditary molecular anomaly of the substances which control of blood coagulative properties

• CLASSIFICATION1. Coagulopathy as a result of isolated deficit of internal

mechanism of prothrombinase activation (haemophylia А, В, С, Willebrand’s dis., Hageman’s deficit)

2. Coagulopathy as a result of isolated deficit of external mechanism of prothrombinase activation (hypoproconvertinemia – deficit of VII c. f.)

3. Combined deficit of internal mechanism and external one of prothrombinase activation (parahaemophylia – deficit of V c. f., Stuart-Prauer’s dis. – deficit of X c. f.)

4. Violation of the last stage blood coagulation (afibrinogenemia)

HEREDITARY CОАGULOPATHY

STATISTIC

• Amount of coagulopathie’s types in general statistic:

Hemophilia А 68 – 78% Willebrand’s disease 9 – 18 % Hemophilia В 6 – 13 % Hemophilia С, parahaemophylia, hypoproconvertinemia 1 – 2 %

Other types are the medical casuistry (occur very rarely)

Hemophilia А

Haemorrhage syndrome caused by hereditary deficit of VIII f. procoagulative unit

Structure of VIII Factor (high mass protein)1. Procoagulative glucoprotein (VIII:C)2. Glucoprotein, which causes thrombocytes adhesion (VIII:WF)3. Glucoprotein, which causes thrombocytes adhesion due to

ristomicine (VIII:R-cоf.)4. Antigen marker of VIII:C (VIII:C АG)5. Antigen marker of VIII:R-cоf (VIII:R АG)

Activity of factors VIII:K and VШ:W is being decreased at the decrease of complex structure mass.

• ETHIOLOGY – gene anomaly in X-chromosome which controls synthrsis of procoagulative glucoprotein (VIII:C)

They ill – males (46, XhY ) – females (46, XhXh ), (45, Xh O) Types; - Hemophilia А+ (antigen positive hemophilia is the result of

abnormal VIII:C factor synthesis), they ill 8 –10 % - Hemophilia А- (antigen negative hemophilia – no synthesis of

VIII:C factor), they ill 90 –92 % Clinical signs: hemorrhages in major joints, deep

hematomas of skin, intramuscular hematomas, massive and prolonged posttraumatic bleedings, intra ubdominal bleedings, in side gastro-intestinal tract

Hemophilia А

• Children of last Russian Car, his sun suffered from hemophilia A.

• ETHIOLOGY – gene anomaly in X-chromosome which controls synth. of IX coagul. f.

They ill – males (46, XhY ) – females (46, XhXh ), (45, Xh O) Types; - Hemophilia B+ (antigen positive hemophilia is the

result of abnormal IX factor synthesis) - Hemophilia B- (antigen negative hemophilia – no

synthesis of IX factor) Clinical signs: hemorrhages in major joints, deep

hematomas of skin, intramuscular hematomas, massive and prolonged posttraumatic bleedings, intra ubdominal bleedings, in side gastro-intestinal tract

Hemophilia B

Hemophilia in newborn

(subcutaneous hematoma)

Subcutaneous hematoma in childe

after injection

Acquired coagulopathy • Character – polydeficit

• ETHIOLOGY 1. immune inhibition of coagulative factor (antigenic

noncompatibility of the mother and the fetus)

2. K-vitamin dependent coagulative factors deficit (VII, X, IX, II) а) poor vitamin K synthesis (dysbacteriosis, profusal diarrhea,

enteropathies ) б) violation of vitamin K absorbtion (obturative icterus) в) damage of the liver

3. heparin or herudin overdose

Hypercoagulation

• Pathological property of the blood which is characterised by trombuses formation inside the

vessels

trombosis

DIC-syndrome

DIC-syndromedisseminated intravascular blood coagulation syndrome

• CLASSIFICATION

• By clinical course 1) acquired

2) chronic

1) local

2) diffuse

ETHIOLOGY

1. Infection , sepsis (bacteriemia, virusemia)2. Chok - traumatic, hemorrhagical, anaphylactic,

cardiogenic, septic (at septic shock death occurs in 100 % cases)

3. Surgical operation4. Thermal burns and chemical ones5. Terminal states (stages of the dying), heart stop6. Acute intravessels hemolysis of the RBC’s 7. Obstetrics pathology (20-25 %)8. Leukemia (33-45 %)9. Immune diseases 10. Allergy reactions

DIC-syndrome stages

• 1) Hypercoagulation (numerous thrombus's formation because hyperactivity of coagulative system)

• 2) Coagulopathy of using (exhaustion of coagulative system, overusing of the thrombocytes for thrombus's formation)

• 3) Hypocoagulation (decrease of coagulative system activity, activation of anticoagulative system and fibrinolysis)

• 4) Finishing (recovery, complications, death)

1) Hyperthrombinemia

(thromboplastin from injured tissues and blood cells comes in to the bloob and conduces thrombin formatting)

DIC-syndrome pathogenesis

At infection active monocytes start to produce such coagulative factors as

VII, X, IX, II

2) Thrombocytes aggregation

(it causes thrombocytopenia of using which results in bleeding)

3) Erythrocyte’s damage and hemolysis

(couses АDP excretion, thrombocyte’s adhesion and aggregation)

DIC-syndrome pathogenesis

4) “Humoral protease detonating ” (activation of coagulative factors,

anticoagulative factors, fibrinolytics, proteins of kallikrein-kinin system, proteins of complement system causes accumulation of great amount of proteins disintegration metabolites in the blood. They are very toxic and damage a vascular wall and tissues)

DIC-syndrome pathogenesis

5) Blood coagulative factors exhaustion (causes bleeding)

6) Exhaustion of coagulative system (results in thrombosis)

DIC-syndrome pathogenesis

1. Hemocoagulative shock (at acute DIC-syndrome)

reason microcirculation violations (causes tissue’s hypoxia) accumulation of proteolysis toxic substances

signs * decrease of arterial pressure * decrease of central venous pressure * development of profusal bleeding (promotes the

transformation of hemocoagulative shock into the hemorrhagic one )

DIC-syndrome clinical signs

2. Нaemostasis violation

1. Hypercoagulation

Main sign – thrombosis

Blood is clotted in test-tube

2. Hypocoagulation

Main sign – bleeding

At the same time exhaustion of fibrinolysis system occurs)

DIC-syndrome clinical signs

3. Thrombocytopenia

results from thrombuses great amount formation in vessels

(Thrombocytopenia of using)

DIC-syndrome clinical signs

4. Block of microcirculation(causes damage of the organ-targets)

- in lungs (thrombuses come from venous system) – results in acute respiratory failure

- in kidneys - acute renal failure- in ventricle and intestine - results in mucous

membrane dystrophy and profusal bleedings, intoxication, chok (high morbidity percentage)

- in suprarenal glands- in liver- in pituitary gland

DIC-syndrome clinical signs

Thank you for attention !