Bleeding disorders
Doc. MUDr. L. Boudová, Ph.D.
Bleeding disorders
I. Vessels - increased fragility
II. Platelets - deficiency or dysfunction
III.Coagulation disorders
IV.Combination I-III
• I. Vessels
• infections, drugs (hypersensitivity)
• poor vascular wall: Ehlers-Danlos, scurvy;
Cushing syndrome, old people
• hereditary hemorrhagic teleangiectasia
• amyloid
Thrombocytes
150-300 000/mm3
normal
100 000/mm3
50 000/mm3
20 000/mm3
thrombocytopenia
posttraumatic bleeding
spontaneous bleeding
Thrombocytopenia
•
•
•
•
decreased production
increased destruction
sequestration
dilution
Splenomegaly
a sign of an underlying disease
a problem per se
bigger spleen~ bigger function
= destruction of blood cells
Hypersplenism
1. splenomegaly
2. (pan) cytopenia
3. 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 microangiopathies
related clinical syndromes
thrombotic thrombocytopenic purpura (TTP)
hemolytic-uremic syndrome (HUS)
ENDOTHELIAL INJURY
WIDESPREAD HYALINE MICROTHROMBI
OVERLAP - common features (TTP, HUS):
• thrombocytopenia
• microangiopathic hemolytic anemia
• fever
Thrombotic microangiopathies
thrombotic thrombocytopenic purpura (TTP)
hemolytic-uremic syndrome (HUS)
Versus
Disseminated intravascular coagulation
Common: hyaline thrombi
!!Differences: DIC: primary importance:
activation of clotting system
Thrombotic microangiopathies
related clinical syndromes
thrombotic 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
HUS
Common: thrombocytopenia, microangiopathic
hemolytic anemia, fever
neurological
deficits
(transient)
renal failure
adult women
mostly no neurol. sympt.
acute renal failure
DOMINANT!
children; E. coli O157:H7,
verotoxin
Microangiopathic hemolytic
anemia
hemolytic-uremic syndrome
several fragmented red cells
Thrombotic microangiopathies
thrombotic thrombocytopenic purpura (TTP)
hemolytic-uremic syndrome (HUS)
Versus
Disseminated intravascular coagulation
Common: hyaline thrombi
!!Differences: DIC: primary importance:
activation of clotting system
Disseminated intravascular
coagulation (DIC)
 secondary complication
of some serious condition
 consumption coagulopathy
 thrombohemorrhagic diathesis
 acute, subacute, chronic
DIC: thrombotic and hemorrhagic
diathesis
activation of coagulation sequence
Microthrombi
hypoxia, infarctions
Consumption →depletion of platelets and
clotting factors
+ secondary activation of
fibrinolysis
hemorrhages
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