Doc. MUDr. Ludmila Boudová, Ph. D.
Pathology - lecture
Bleeding disorders
vessels – increased fragility
platelets: deficiency or dysfunction
coagulation disorders
Vessels (see the textbook for details)
infections
drugs
scurvy, Ehlers-Danlos
old people
Henoch –Schoenlein
Hereditary hemorrhagic teleangiectasia
amyloid infiltration of blood vessels
Thrombocytopenia
normal range: 150 – 300 000 /mm3
below 100 000 mm3: thrombocytopenia
spont. bleeding: below 20 000
below 50 000 – posttraumatic bleeding
main manifestation: bleeding – mainly from small vessels, skin, mucous membranes (GIT,
genitourinary)
The small punctate bleedings: petechiae
danger: intracranial bleeding
decreased production
diseases affecting the whole BM
aplast. anemia, marrow infiltration
selective impairment of platelet production
drug-induced, alcohol induced, infections
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Doc. MUDr. Ludmila Boudová, Ph. D.
Pathology - lecture
ineffective megakaryopoiesis (megaloblastic anemia, paroxysmal nocturnal hemoglobinuria)
decreased platelet survival
destruction:
immunologic -
autoimmune (ITP), SLE - autoantibodies
isoimmune (post-transfusion, neonatal) - alloantibodies
drug-associated (heparin, quinidin)
infections (EBV, HIV, CMV)
non-immunologic
DIC
TTP
giant hemangiomas
microangiopathic hemolyzic anemia
sequestration - hypersplenism
dilutional – in the transfused blood platelets do not survive longer than 24 hours – massive
transfusions lead to thrombocytopenia
ITP – autoimmune (immune thrombocytopenic purpura)
acute – children after infection, resolution within 6 months
chronic: SLE, viral infections, drugs
improves after splenectomy – major site for the removal of the sensitized platelets and of
autoantibody production
hemorrhages: skin, mucosae; rarely: brain!
Drug-induced thrombocytopenia
PNC, heparin, antimalarials
mild (shortly after administration) or severe (1-2 weeks after the beginning of the therapy)
Thrombocytopenia in HIV
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Doc. MUDr. Ludmila Boudová, Ph. D.
Pathology - lecture
the most common hematologic manifestation of HIV infection
Thrombotic microangiopathies
inciting event: endothelial injury
hyaline thrombi in small vessels –platelets consumed – thrombocytopenia
microthrombi – block fully or partially the vessels - may form bridges – red cells may get
sheared – hemolysis – anemia
block of vessels: ischemia
Thrombotic thrombocytopenic purpura – adult women – thrombocytopenia,
hemolytic anemia, renal failure, neurologic symptoms, fever; very dangerous! may be cured
HUS (haemolytic-uraemic syndrome)– children, after gastrointestinal infection
caused by E. coli O157:H7 – verotoxin, defective platelet function – congenital or acquired
Congenital:
1. adhesion to subendothelial collagen – Bernard Soulier – AR, deficiency of plt membrane
complex - receptor for vWF
2. aggregation – thrombastenia – AR – deficiency of fibrinogen receptor – fail to aggregate
3. platelet secretion – release of PG and granule-bound ADP impaired
Acquired:
aspirin, NSARFD – inhibitor of cycloxygenase – suppress the production of PG –normally
involved in PLT aggreg. and release reaction
uremia – abnormalities of plt functions
Clotting factors
bleeding after injuries (even minute injuries), after surgical procedures
her.: one factor – VIII – hem A, IX (Christmas dis.) – IX – both GR
acquired: multiple – vitamin K deficiency – decreased synthesis of F II, VII, IX, X, protein C
DIC
liver disease
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Doc. MUDr. Ludmila Boudová, Ph. D.
Pathology - lecture
Hemophilia A
reduction in the amount or activity of F VII – cofactor for activation of F X in the intrinsic
coagulation cascade
males, (homozygous women; heterozygous women: unfavorable lyonization)
variable degrees of deficiency and of clinical severity, different types of mutations (less than
1% of normal activity: severe)
Clin: easy bruising, massive bleeding after injury(oper.)
joints – crippling
no petechiae
bleeding
antibodies against the factor, transmission of the infection
Hemophilia B – Christmas
clinical appearance: like hem. A (assay of the factors)
von Willebrand disease
very common, 1% of population, variants, some affect: quantity, some: quality of vWF,
concerns: PLT function and coagulation pathway
vWF and FVIII circulate in the plasma as a unit – promotes clotting
PLT adhesion to subend. collagen
spont. bleeding from mucous membranes, excessive bl.- after injury, menorrhagia (prolonged
bleeding time, normal plt counts)
DIC
consumption coagulopathy – always secondary, caused by other serious conditions
increased activation of coagulation in the small vessels - widespread, diseminated - thrombi
This tendency– thrombotic diathesis –-- ischemia, infarction
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Doc. MUDr. Ludmila Boudová, Ph. D.
Pathology - lecture
in these thrombi - PLT, coagulation factors and fibrin consumed –a lack of them - and,
secondarily, a bleeding tendency (then, also pathologically activated fibrinolysis – worsens
the bleeding)
tendency to thrombosis and to bleeding combine – difficult treatment (heparin, FFP, PLT
acute – most cases – onset fulminant
subacute, chronic – carcinoma. retention of dead fetus
Mechanisms triggering DIC:
- release of tissue factor or of thromboplastic substances into the circulation
- widespread injury to the endothelium
Main disorders leading potentially to DIC
I. Obstetrics (50%)
1. Abruptio placentae
2. retained dead fetus
3. septic abortion
4. embolism of amniotic fluid
5. toxemia
II. Infections - sepsis
III.
Traumas, burns, surgery
IV.
Neoplasms (one third of DIC cases)– carcinoma – mucus producing – lung, pancreas,
stomach; AML
Morphology: thrombi may be everywhere (brain, heart,,) – sometimes everywhere,
sometimes illogical distribution; lungs – often also hyaline membranes )
kidney – acute renal failure, failure of circulation, shock, hemorrhages
adrenals: massive bleeding – meningococcemia – Waterhouse-Friderichsen syndrome
pituitary – Sheehan – necrosis, hemorrhages
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Doc. MUDr. Ludmila Boudová, Ph. D.
Pathology - lecture
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