Bleeding disorders

Doc. MUDr. L. Boudová, Ph.D.

Bleeding disordersI. Vessels - increased fragilityII. Platelets - deficiency or dysfunctionIII.Coagulation disordersIV.Combination I-III

• I. Vessels • infections, drugs (hypersensitivity) • poor vascular wall: Ehlers-Danlos, scurvy;

Cushing syndrome, old people• hereditary hemorrhagic teleangiectasia• amyloid

Thrombocytes150-300 000/mm3 normal

100 000/mm3 thrombocytopenia

50 000/mm3 posttraumatic bleeding

20 000/mm3 spontaneous bleeding

Thrombocytopenia

• decreased production

• increased destruction

• sequestration

• dilution

Splenomegaly

a sign of an underlying diseasea problem per se

bigger spleen~ bigger function = destruction of blood cellsHypersplenism1. splenomegaly2. (pan) cytopenia3. correction of blood cytopenia by

splenectomy

Immune thrombocytopenic purpura

Idiopathic TP – but autoimmune!

Antibodies against platelets

Primary or secondary

ITP• Acute – children

• Abrupt onset, both sexes, 2 weeks after virosis, resolves within 6 mo, 20% chronic

• Chronic – adults (F:M 3:1)

• Petechial hemorrhages and ecchymoses

• Easy bruising, skin, mucosa, nose, gums, soft tis., melena, hematuria, menstruation

• Clin.: nonspecific – reflective of thrombocytopenia

ITP - organs

• Spleen - normal size

• PB: megathrombocytes

• BM:+ /- more megs

• Therapy: splenectomy

Thrombotic microangiopathiesrelated clinical syndromesthrombotic thrombocytopenic purpura (TTP)hemolytic-uremic syndrome (HUS)

ENDOTHELIAL INJURY WIDESPREAD HYALINE MICROTHROMBI

OVERLAP - common features (TTP, HUS):

• thrombocytopenia

• microangiopathic hemolytic anemia

• fever

Thrombotic microangiopathiesthrombotic thrombocytopenic purpura (TTP)hemolytic-uremic syndrome (HUS)

VersusDisseminated intravascular coagulation

Common: hyaline thrombi

!!Differences: DIC: primary importance:

activation of clotting system

Thrombotic microangiopathiesrelated clinical syndromesthrombotic thrombocytopenic purpura (TTP)hemolytic-uremic syndrome (HUS)

ENDOTHELIAL INJURY WIDESPREAD HYALINE MICROTHROMBI

OVERLAP - common features (TTP, HUS):

• thrombocytopenia

• microangiopathic hemolytic anemia

• fever

Thrombotic microangiopathies

TTP

neurological deficits (transient)

renal failureadult women

HUS

mostly no neurol. sympt.acute renal failure DOMINANT!children; E. coli O157:H7, verotoxin

Common: thrombocytopenia, microangiopathic hemolytic anemia, fever

Microangiopathic hemolytic anemia

hemolytic-uremic syndrome several fragmented red cells

Thrombotic microangiopathiesthrombotic thrombocytopenic purpura (TTP)hemolytic-uremic syndrome (HUS)

VersusDisseminated intravascular coagulation

Common: hyaline thrombi

!!Differences: DIC: primary importance:

activation of clotting system

secondary complication

of some serious condition consumption coagulopathy

thrombohemorrhagic diathesis

acute, subacute, chronic

Disseminated intravascular coagulation (DIC)

DIC: thrombotic and hemorrhagic diathesis

Microthrombi hypoxia, infarctions

Consumption →depletion of platelets and clotting factors

+ secondary activation of fibrinolysis

hemorrhages

activation of coagulation sequence

Mechanisms of DIC trigger

1. Release of tissue factor or thromboplastic substances

2. Widespread endothelial injury

DIC

1. obstetrics – 50%; abruptio placentae, retained dead fetus, septic abortion, amniotic fluid embolism, toxemia

2. neoplasms – 30%; adenocarcinomas, AML

3. infections – gram-negative sepsis

4. trauma, burns, extensive surgery

5. Other – snakebite, heat stroke, giant hemangioma, aortic aneurysm etc.

DIC

• Morphology microthrombi

• Kidneys hemorrhages

Microinfarcts, bilat. renal necrosis

• lungs

• Brain - microinfarcts, hemorrhage

• Placenta

• Spleen , liver

• Endocrine organs: pituitary, adrenals

DIC - clinical

• microangiopathic hemolytic anemia, RDS – dyspnea, cyanosis

• neurologic symptoms, oliguria, acute renal and circulatory failure,

• Convulsions, coma

• SHOCK

Disseminated intravascular coagulation

hyaline thrombi

Sy Waterhouse - Friedrichsen