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RED BLOOD CELLS DISORDERS: ANEMIAS, POLYCYTEMIA. BLEEDING
DISORDERS.
 ANEMIA
= is a reduction in the oxygen transport capacity of blood, usually due to a
reduction of total amount of circulating red cells
- anemia is characterized lower than normal hematocrit (=ratio of
erythrocytes to plasma- normal 40:60, normal hematocrit is about 42-50%,
hematocrit is an important determinant of blood viscosity)
-lower than normal hemoglobin concentrations
-increased erythropoiesis- due to increased production of
erythropoetin-in most anemias-causes erythroid bone marrow hyperplasia,
increased erythropoiesis may also occur in the spleen and liver -sites of
possible extramedullary hemopoiesis
 CLASSIFICATION OF ANEMIAS -is based on the mechanism
I. - anemias due to decreased erythropoiesis
II. -anemias of blood loss -acute -chronic
III. -anemias due to increased rate of destruction of erythrocytes (hemolytic
anemias)
1./ intrinsic (intracorpuscular) abnormalities of RBCs -hereditary,
acquired
2./ extrinsic (extracorpuscular) abnormalities
Clinical features of anemias:
-characterized by pallor of the skin and mucous membranes
-by symptoms that represent a manifestation of hypoxia (=decreased
oxygen content of the blood)- fatigue, breathlessness
-myocardial hypoxia may result in angina pectoris pains, even cardiac
failure
-decreased hemoglobin level
identification of the type of anemia - requires examination of peripheral
blood and of the bone marrow specimen
 ad I./ ANEMIAS DUE TO DECREASED ERYTHROPOIESIS
-impaired RBCs production may be caused by a variety of disorders
major pathogenetic groups of anemia caused by a decreased erythropoiesis
1. Aplastic anemias
2. Anemias caused by bone marrow replacement
3. Anemias due to defective synthesis of DNA
4. Anemias due to defective hemoglobin synthesis
 1./ APLASTIC ANEMIA
-is due to failure of production, or due to suppression or destruction of
stem cells in BM, which leads to decreased generation of RBCs- anemia
failure of production of RBCs, granulocytes and platelets= pancytopenia
BM shows decrease of cellularity
etiology:
-may be idiopathic - no identifiable cause
-drugs- is by far the most common known cause of aplastic anemiadamage to the BM may be dose-related and predictable (alkylating agents,
antimetabolites, such as vincristin, busulfan)
or idiosyncratic and thus unpredictable, such as caused by
chloramphenicol, chlorpromazine, streptomycin
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-irraditaion
-some infections or inherited diseases, like Fanconi anemia, which is
associated with multiple congenital anomalies
pathogenesis:
-in idiopathic cases, the stem cell failure may be due to primary structural
defect of stem cells (BMT)
-or mediated by immune-suppression of the stem cells, then may be reversed
by immunosuppression therapy
morphology:
-bone marrow is hypocellular - active BM is replaced by fat cells
clinically:
-all symptoms are related to pancytopenia
-leading feature is usually bleeding diathesis
 2./ ANEMIAS DUE TO BM REPLACEMENT
a) involvement of the bone marrow cavity by malignant tumors
-most often-in leukemias- malignant neoplastic proliferations of
hematopoietic cells
- infiltration of BM by malignant lymphoma- neoplastic proliferation
derived of lymhpoid cells arising most often in lymph nodes
- infiltration by metastatic carcinomas, such as breast ca,
bronchogenic ca, etc
b) replacement of the BM by fibrosis
- in osteomyelofibrosis
 compensatory phenomen include
-extramedullary hematopoiesis - development of active marrow in sites
outside the bone marrow cavity- (spleen,liver)
-release of cells from the marrow before maturation is complete
-results in „shift to left“- implies a release of immature white cells including
the band forms and even of myeloblasts and myelocytes and normoblasts (
nucleated RBCs ) into the peripheral blood
 3./ ANEMIAS DUE TO DEFECTIVE SYNTHESIS OF DNA=
MEGALOBLASTIC ANEMIAS
megaloblastic anemias - are characterized by disorder in maturation phase
of erythropoiesis resulting in formation of abnormal erythroid precursors
which are enlarged and show failure of maturation - these are called megaloblasts
etiology:
-megaloblastic anemias result from conditions in which DNA synthesis
in erythropoiesis is abnormal, for example due to
-vitamin B 12 deficiency
-folic acid deficiency
Both play role as cofactors in the synthesis of DNA (intrinsic factor=
produced by mucosa cells in the stomach- enables B12 vitamin to be
absorbed properly from the food)
-vitamin B12 is present in high concentrations in the liver and meat of
animals, but is absent of plants- dietary B12 vitamin deficiency is rare,
except of strict vegeterians
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-folic acid is present in most vegetables- dietary deficiency is more commonin many states of malnutrition
there are two principal forms of megaloblastic anemias
a) anemia due to B12 deficiency
b) anemia due to folic acid deficiency
 a) Anemia due to B12 deficiency - has several possible causes, including
so-called
A) PERNICIOUS ANEMIA
-is a form of megaloblastic anemia due to B12 deficiency
-it is common in western Europe and in the U.S. but is rather rare in
Asia and Africa
-PA - occurs predominantly after the age of 50
-slightly more often in males
pathogenesis
-is an autoimmune disease caused by immunologic destruction of the
gastric mucosa
microscopically: - the mucosa of the body and the fundus of the stomach is
characterized by diffuse lymphocytic infiltration and progressive loss of
parietal cells
chronic atrophic gastritis
-associated with a failure of secretion of acid (achlorhydria) and
intrinsic factor- leads to drastic reduction of B12 vitamin absorbtion
pathologic and clinical features in PA:
-chronic atrophic gastritis-achlorhydria-failure of intrinsic factor
secretion-leads to B12 vitamin deficiency
-megaloblastic anemia
-neurologic abnormalities due to demyelination (pathogenesis not
clear)
very characteristic-subacute combined degeneration of the spinal cord (
demyelination of the posterior and lateral collumns of the cord )
-leads to loss of position and vibration sense to loss of tendons reflexes
-peripheral neuropathy due to demyelination of nerves
treatment -replacement therapy by injected B12 vitamins- anemia improves
rapidly and completely, neurologic symptoms slowly and incompletely
-precancerous epithelial dysplasia in chronic atrophic gastritis- can be
detected by gastric mucosa biopsy
other causes of B12 vitamin deficiency different from PA include:
-inadequate dietary habits- only in strict vegetarians
-total gastrectomy
-Crohn disease- chronic idiopathic inflammatory large bowel disease
-surgical removal of terminal ileum, -by-pass of terminal ileum - B12
vitamin complexed to intrinsic factor is normally absorbed in terminal ileum
-severe bacterial infection of large intestine
 B) ANEMIAS DUE TO FOLIC ACID DEFICIENCY
-has several underlying causes including
-inadequate intake in food- in chronic alcoholism, in severe
malnutritions
-due to failure of absorbtion- in malabsorbtive syndromes, such as
tropical sprue, coelic disease
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-in states of increased demand, such as in pregnancy, in malignant
tumors- due to increased synthesis of DNA in malignant cells
-anticancer drugs- such as methotrexate - have antagonistic effect to
folic acidPathologic findings in all megaloblastic anemias:
-RBCs changes- most apparent- erythropoiesis changes from
normoblastic to megaloblastic
megaloblast - larger than normoblast, shows delayed maturation but
normal cytoplasmic hemoglobinization, primitive nucleus and fully
hemoglobinized cytoplasm
-changes in BM- accumulation of erythrocyte precursor cells - BM is
hypercellular- resembles acute blastic leukemia
-changes in peripheral blood- shows macrocytosis- large RBCs with
anisocytosis-marked variation in size poikilocytosis-marked variation in
shape
-changes in neutrophils- neutrophil precursors in the BM show
enlargment- giant metamyelocytes are characteristic in peripheral bloodhypersegmented nuclei in lekocytes
-changes in other cells- disorder in DNA synthesis affects
predominantly those cells with high rate of cell turnover ( intestinal
epithelium- enlarged nuclei )
Clinical symptoms in megaloblastic anemias
-severe anemia
-macrocytosis and hypersegmented leukocytes in peripheral blood
-bone marrow examination reveals hypercellularity- megaloblastic
erythroid hyperplasia
 4./ ANEMIAS DUE TO DEFECTIVE HEMOGLOBIN SYNTHESIS
includes three major clinicopathologic entities
a) iron deficiency anemia
b) anemia in chronic diseases
c) sideroblastic anemia
 A) IRON DEFICIENCY ANEMIA
-is by far most common type of anemia worldwide
Causes of iron deficiencies
-iron deficiencies due to dietary deficiency- most common in
underdeveloped countries
-increased demand of iron- in growth phase in early infancy or in
adolescence in pregnancy and lactation
-malabsorbtion of iron- in severe generalized states (coelic disease,
tropical sprue, etc)
-after total gastrectomy- gastric acid is necessary for complete
absorbtion of iron
-chronic blood loss- major cause of iron deficiency anemia results
either from
-occult GIT blood loss due to hookworm infection- small
parasitic intestinal worm (ancylostomiasis)= disease characterized by
anemia, GIT pains, weakness -(larvae enter the body through the skin)
-occult GIT bleeding due to chronic ulcers, cancers,
hemorrhoids, esophageal varices
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Pathologic findings:
-in iron deficiency- the first symptom- decreased serum level of ferritinreflects the level of storage of iron -absence of iron in BM specimens
when iron stores are exhausted- the serum iron level falls
-anemia is due to both a decresed amount of hemoglobin in individual
RBC ( erythrocytes are poorly hemoglobinized) and decrease of total amount
of RBCs
erythrocytes are small- microcystosis- hypochromic microcytic anemia
-bone marrow changes- shows variable normoblastic hyperplasia
-storage iron is absent
-epithelial changes- result in atrophy of many epithelial surfaces, such
as mucous membranes of the mouth, tongue, stomach
Plummer-Vinson syndrom= iron deficiency anemia+ atrophic glossitis+
dysphagia +koilonychia (concave fingernails)
treatment: -iron replacement therapy and to find and correct the reason for
anemia (ulcers, cancers)
 B) ANEMIAS IN CHRONIC DISEASES
-in chronic renal failure- normochromic normocytic anemia due to
failure of normal secretion of erythropoetin in the kidney
-BM shows mild erythroid hyperplasia
 C) SIDEROBLASTIC ANEMIA
-is uncommon type of anemia characterized by the presence in the BM
of increased numbers of sideroblasts= erythroid precursors with iron in their
cytoplasm
-it has a variety of possible causes both primary and secondaryprimary - may be inherited or acquired (of unknown causes)
secondary- in chronic alcoholism, due to drugs, such as chloramphenicol,
poisoning- chronic lead poisoning
Pathologic findings:
-SA is characterized by hypochromic microcytic or dimorphic anemia,
it means that in the PB- mixture of normal erythrocytes, microcytes and
macrocytic erythrocytes
serum iron level increased
pathogenesis:
defect in incorporation of iron into the hemoglobin molecule
 II. ANEMIA OF BLOOD LOSS
-acute- acute hemorrhage results in a loss of whole blood leading to
hypovolemia- equivalent amounts of RBCs, white cells and serum are lostthus, main blood values are normal- at first stage
-within hours- water retention (important compensatory mechanism
for hypovolemia) - results in decrease of RBCs count, decrease of hemoglobin
concentration, decrease of hematocrit in PB
-regeneration of erythrocytes- bobe marrow shows erythroid
hyperplasia
anemia is temporary, body iron storage is replenished over the next few
months
-chronic- chronic bleeding is compensated by erythroid hyperplasia of
BM until Fe stores are exhausted -after this point- iron deficiency anemia
develops
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 III.HEMOLYTIC ANEMIA- due to increased rate of destruction of RBCs
-group of diseases characterized by shortened survival of RBCs in PB
RBCs destruction occurs
EXTRAVASCULAR HEMOLYSIS-is characterized by
-1.-hemolytic jaundice-increased production of unconjugated
bilirubin because of increased breakdown of hemoglobin
-unconjugated bilirubin is complexed with plasma albumintransported to the liver- taken up by liver cells-jaundice develops when the
amount of unconjugated bilirubin delivered to the liver exceeds the capacity
of the liver to conjugate
-2.-increased level of bilirubin in bile- the liver excretes increased
amounts of conjugated bilirubin into the bile- bilirubin pigment stones
formation in the gallbladder
-3.-increased amount of urobilinogen- in urine, in large intestine
content
-4.-erythroid hyperplasia- BM shows hyperplasia- expansion of BM
cavities- increased erythropoiesis results in release of reticulocytes into PB
-5.-hemosiderosis-degradation of hemoglobin from the destroyed
RBCs- deposition of hemosiderin ( spleen, liver)
INTRAVASCULAR HEMOLYSIS is characterized by
-1.-hemolytic jaundice- unconjugated bilirubinemia
-2.-erythroid hyperplasia- in chronic hemolysis only
-3.-hemoglobinemie free hemoglobin in plasma appear when
hemolysis has exhausted the capacity of plasma haptoglobin to bind
hemoblobin
-4.-hemoglobinurie -hemoglobin molecule may pass the glomuruli
 CLASSIFICATION OF HEMOLYTIC ANEMIAS
1) intrinsic defects of erythrocytes (intracorpuscular anemia)
a- hereditary1- RBC membrane disorders or cytoskeleton disorders
-spherocytosis
-eliptocytosis
2- RBC enzyme deficiency
-G-6-PD
(glucose-6-phosphatase-dehydrogenase
deficiency)
3- hemoglobinopathies- hemoglobin synthesis disorders
- thalassemias
-sickle cell anemia
b-acquired hematologic diseases
- PNH
2) hemolysis due to extrinsic factors (extracorpuscular anemias)
immune anemia
other causes
ad 1) intrinsic defects of erythrocytes
ad 1a) hereditary:
 HEREDITARY SPHEROCYTOSIS
-is congenital autosomal dominant disease with variable penetrance
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-patients may present with severe hemolysis in childhood or mild hemolysis
in adult age
-is characterized by change in shape of RBCs from the normal biconcave
shape to a spherical shapepathogenesis: proteins of red cell membrane are defective in structure or
reduced in amount- results in reduction of cell surface- causes that RBCs
assume a spheroidal shape
-spherical RBCs are more fragile- increased fragility - spherocytes are more
susceptible to lysis- s. show autohemolysis- when incubated at 37 C for 2448h
-life span of spherocytes is shortened- destruction occurs in the spleen
clinical features:
-patients present with anemia and jaundice
-splenic enlargement- histologically splenic cords of Billroth are
markedly congested and exhibit prominent erythrophagocytosis
-peripheral blood- shows spherical microcytes
-bone marrow shows normoblastic hyperplasia
-aplastic crisis may occur rapidly-associated with acute infection
treatment:
splenectomy- removal of the site of maximum erythrocyte destruction
ad 2 ) GLUCOSE-6-PHOSPHATASE-DEHYDROGENASE DEFICIENCY (G6PD)
-most common erythrocyte enzyme deficiency- RBCs are more
vulnerable to oxidants
-it is a X-linkedinherited anomaly-full expression of deficiency occurs in
males
hemolytic attacks trend to affect older RBCs
clinically: -most patients are asymptomatic, but acute intravascular
hemolysis may occur due to exposure of oxidant drugs, such as sulfonamide,
nitrofurantoin, etc.
-rarely patients develop mild chronic hemolytic anemia
ad 3 ) hemoglobinopathies
1.- THALASSEMIAS
-is a heterogenous group of congenital disorders, characterized by a lack or
decreased rate of synthesisof either normal alfa- or the beta chains of
hemoglobin A
thalasemias are more common in Mediterranean, in Africa and Southeast
Asia
beta-thalassemia- decrease of synthesis of beta-globin- free alfa chains
form highly unstable aggregates - cell membrane damage- destruction of
RBC precursors
alfa-thalassemia- inbalance in sxynthesis of alfa chain
morphology:
-in peripheral blood- microcytic anemia with marked anisocytosis
-in bone marrow- ineffective erythropoeisis - due to destruction of RBC
precursors in BM- erythroid hyperplasia
-in spleen- hemolysis of abnormal RBCs- activation- splenomegaly
-positive iron balance due to increased absorbtion of iron in the
intestine and due to transfusions- lead to severe iron overload- secondary
hemochromatosis- myocardial or liver failure
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2.- SICKLE CELL DISEASE
-is a hereditary hemoglobinopathy caused by a single point mutation
of the globin gene- that causes a replacement of aminoacids, of normal Hb
glutamic acid for valine in beta chain -results in formation of hemoglobin-S
morphology:
-occurrence of so-called sickle cells- erythrocytes of pathologic shape, that
under decreased oxygen lead to formation of so-called tactoids
-deformation of RBCs and decreased solubility of hemoglobin
initially sickling can be reversed to normal shape-when oxygenation
improves later, however, the shape of RBCs becomes permanent
increased phagocytosis and destruction of the RBCs in the spleen
clinically:
onset in early childhood- death in young adult age
-patients present with chronic extravascular hemolysis and severe
anemia- chronic hemolytic state-sicle cells have rigid membranes- prone to
sequestration
-growth retardation
-mild hemolytic jaundice
-there is also tendency to microvascular occlusions- because sicle cells
have a propensity to adhere to capillary endothelium
BM shows marked hyperplasia- compensatory normoblastic
complications:
aplastic crisis- may cause sudden failure of hematopoiesis- may be due to
acute infection, drugs, other causes
hemosiderosis-due to multiple blood transfusions
and because of stimulation of absorbtion of iron in the intestine
vaso-occlusive crisis- is due to filling the microcirculation by aggregates of
sickle cells- cause multiple small infarctions-painful episodes of ischemic
necroses
fever, ischemic pains-heart, skeletal muscels, bones-aseptic bone necrosis
splenic changes-are characteristic- enlargment, and due to repeated
infarctions- multiple small scars with heavy hemosiderin deposition- called „
autosplenectomy“thus the patients have higher propensity to infections
ad 1b)- acquired:
PAROXYSMAL NOCTURNAL HEMOGLOBINURIA ( PNH)
-is a rare acquired disease of RBCs characterized by an increased
sensitivity of RBC membrane to complement-results in chronic intravascular
hemolysis
-complement activation may occur in vivo during sleep-because of decreased
pH-due to slower respiration- results in paroxysmal nocturnal Hb-uria
-patients are young, anemia may be severe
pathogenetically related to aplastic anemia-PNH represents a clone of
abnormal erythrocytes developing in hypoplastic BM
2) hemolysis due to extrinsic factors (extracorpuscular anemias)
1- anemias mediated by antibodies- both autoimmune and
isoimmune
2- mechanical trauma to RBCs
3- infections
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4-chemical injury of RBCs- like lead poisoning
5- sequestrations of RBCs- for example in hypersplenism
ad1.- IMMUNE-MEDIATED HEMOLYTIC ANEMIAS
among immune-mediated anemias, there are two major pathogenic groupsautoimmune and isoimmune
AUTOIMMUNE HEMOLYTIC ANEMIAS
-group of diseases in which hemolysis occurs as a result of the
presence of auto-antibodies againts blood group associated antigens
-idiopathic warm autoimmune hemolytic anemia
-idiopathic cold autoimmune hemolytic anemia
-paroxysmal cold hemoglobinuria
ISOIMMUNE HEMOLYTIC ANEMIAS
-are those in which the RBCs are destroyed as a result of the activity of
antibodies of another person,
-in blood tranfusion of incompatible blood - hemolytic reaction is rapid
-if severe - intravascular hemolysis results in hemoglobinemia
such patient develop rapid shock- risk of death
-less severe reactions due to non-complement-fixing antibodies
- hemolytic disease in newborn -due to Rh incompatibility
-drug induced hemolysis- may use several possible mechanisms
induction of antibodies- metyldopa
or drug complexes with RBC membrane and this complex becomes
antigenic- penicilin,cephalosporines
ad 2.- mechanical trauma to RBCs
MICROANGIOPATHIC HEMOLYTIC ANEMIAS
-is caused by fragmentation of RBCs as they pass abnormal
microcirculation
-in DIC- fibrin strands- fragmentation of RBCs- hemolysis result in
-1) hemolytic uremic syndrome
-2) thrombotic thrombocytopenic purpura
-in abnormal blood vessels- in malignant hypertension
-in giant capillary hemangioma and malignant blood vessel tumors
-in prosthetic valves- causes trama to RBC,
ad 3.- HEMOLYSIS CAUSED BY INFECTION
-several possible mechanisms may be involved including
-development of autoimmune hemolysis (infective mononucleosis,
mycoplasma infections)
-production of hemolytic toxins (clostridia, streptoccoci)
-direct infection of RBCs -in malaria- red blood cell lysis occurs in
attacks when a release of merozoites from infected RBCs occurs
(Plasmodium vivax)
fever, splenomegaly,
BLEEDING DISORDERS
- disorders characterized by an increase in tendency for bleeding, may be
caused by
I.-increased fragility of blood vessels
II.-disorders of platelets
III.-defects in coagulation
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I. DISORDERS DUE TO INCREASED VASCULAR FRAGILITY
-disorders in this group are relatively common, but usually do not
cause serious bleeding
-most of them result in multiple petechiae or purpuric hemorrhages
-platelet count is normal
possible conditions resulting in this type of bleeding diathesis include:
-infections- underlying mechanismes are vasculitis or DIC
-drug reactions-often mediated by immune complexes in the
vessel walls with production of a acute vasculitis
Henoch-Schonlein purpura- a systemic hypersensitive reaction of unknown
cause, characterized by abdominal pains, polyarthralgia, acute
glomerulonephritis- associated with deposition of immune complexes
II.-DISORDERS OF PLATELETS
A) decrease in number of platelets -THROMBOCYTOPENIA
B) defective function of platelets
THROMBOCYTOPENIA
=decrease in platelet number ( normal count 150-300 thousands per
mm3)- decrease to 10 thousands and lower levels causes bleeding tendency
-characterized principally by petechial bleeding- most often from small
vessels of the skin and mucous membranes
possible causes include:
-decreased production of platelets- occurs in generalized
diseases of the BM, such as in aplastic anemia,disseminated cancer,
leukemias
-decreased platelet survival-results from immunologically
medited destruction of platelets- may follow drug administration, such as
methyldopa or infections, for example AIDS
-there is compensatory megakaryocytic hyperplasia
-sequestration-may occur in the presence of splenomegaly -the
syndrom is called hypersplenism
-splenectomy can cure
most common clinicopathological entities associated with thrombocytopenias
are:
1.-IDIOPATHIC THROMBOCYTOPENIC PURPURA (ITP)
-is associated with immunologically mediated destruction of platelets two
forms are recognozed:
acute ITP -is a self-limited disorder- most common in children after
viral infections ( viral hepatitis, infectious mononucleosis, rubeolla,
cytomegalovirus infections, etc. )
-platelet destruction is probably caused by antigen-antibodies complexes,
directed against viruses, absorbed however on platelets
chronic ITP -destruction of platelets results directly from the presence
of anti-platelets antibodies
-in most patients the platelet-associted IgGs can be identified
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-destruction of antibody-coated platelets occurs in the spleen-splenectomy is
beneficial for more than 80% of patients
clinical features of ITP:
-chronic ITP occurs most often in women, of medium age
-it may be associated with other autoimmune disorders, such as
autoimmune hemolytic anemia,systemic lupus erythematodes,etc.
-most commonly slowly progressive course, with petechial chronic
bleeding, such as nose bleed, but sometimes more serious complications like
for example melena, hematuria or intracerebral hemorrhages may appear
2.- ISOIMMUNE THROMBOCYTOPENIA
-group of disorders that result from development of antibodies directed
againts specific platelet antigens
-after transfusions
-neonatal thrombocytopenia- similar pathogenesis as in fetal
erythroblastosis ( platelet-antigen-negative mother carrying antigen-positive
baby develop antibodies againts platele-antigen that may cross the placfenta
and cause thrombocytopenia in the newborn
3.- THROMBOCYTIC THROMBOCYTOPENIC PURPURA (TTP)
-rare disorder characterized by thrombocytopenia, microangiopathic
hemolytic anemia and fever, neurologic symptoms and renal failure
-most clinical symptoms are due to formation of multiple hyaline
microthrombi
pathogenesis immunologic reaction is directed against endothelial cells,
results in pathologic aggregation of platelets- formation of microthrombi- in
contrast to DIC, activation of clotting system is not primary
clinically:
more commonly in females- peak age about 40years of age
treatment with corticosteroids
IIB.HEMORRAGIC DISORDERS RELATED TO DEFECTIVE PLATELET
FUNCTION
-characterized by prolonged bleeding time associated with normal
platelet count may be congenital or acquired
congenital -there may be defects in platelet adhesion (congenital
deficiency of platelet-membrane glycoprotein)
or defects in platelet secreting activity-platelet cannot produce
prostaglandins, etc.
acquired- many possible conditions, of which two are of clinical
importance
aspirin is known to supress the synthesis of thromboxane which is
necessary for platelet aggregation- used in supplementary treatment of IM
bleeding in uremic patients may be partly due to defects in platelet function
III.HEMORRHAGIC DIATHESIS DUE TO ABNORMALITIES IN CLOTTING
FACTORS
-bleeding seen in patients with abnormalities in clotting system in contrast
to bleeding in platelet deficiencies is characterized by
-more often the bleeding is not spontaneous, more likely
develops after injury or surgical procedure, but is usually serious, with
prolonged bleeding and large hematomas and hemorrhages
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-most common sites of bleeding is the GIT, urinary tract and
particularly large joints and the soft tissues in their vicinity
-clotting abnormalities may be due both to hereditary disorders, such
as in hemophilia and von Willebrand Disease- it was already mentioned
before
or may be acquired-most important clinical settings in this respect are the
vitamin K deficiency, most often caused by liver failure and DIC- that
produces a deficiency of multuple coagulation factors
DISSEMINATED INTRAVASCULAR COAGULATION (DIC)
-is an acute, subacute or chronic thrombohemorrhagic disorder
occurring as a secondary complication of a variety of diseases:
-is characterized by activation of the clotting system leading to
formation of multiple microthrombi throughout the microcirculation- the
consequence of which is consumption of platelets, fibrin and coagulative
factors, secondarily leading to activation of fibrinolytic system
thus, the DIC presents with
-signs and symptoms related to infarctions caused by microthrombi
-signs of hemorrhagic diathesis due to depletion of the elements
necessary for hemostasis and even due to secondary activation of fibrinolytic
processes
pathogenesis:
there are two major mechanisms by which the DIC may be triggered:
1) release of tissue factors and thromboplastic substances into the
circulation
-these substances may be derived from various sources, such as
placenta in various obstetric complications, bacterial endotoxins,
particularly in gram-negative sepsis, etc.
2) widespread injury to the endothelium -endothelial injury can initiate DIC
by causing release of thromboplastic factor from endothelial cells, by
promoting the platelet aggregation, by activating the intrinsic pathway of
clotting cascade
-this endothelial injury may be produced by depositions of antigenantibodies complexes
morphology:
-microthrombi with infarctions in multiple organs and hemorrhages
clinically significant changes are encountered in :
kidneys- thrombi in glomeruli and renal cortical microinfarcts
lungs- microthrombi in alveolar capillaries- may cause clinnically acute
respiratory distress syndrome
brain- microinfarcts and fresh hemorrhages
placenta-widespread thrombi
clinical features:
about 50% of patients with DIC are abstetric patients with complications of
pregnancy
- sepsis and major trauma- rest of patients
other causes- rare
major clinical manifestations of DIC:
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-microangiopathic hemolytic anemia resulting from microvascular
occlusions
-respiratory symptoms including cyanosis, dyspnea
-neurologic symptoms including convulsions
-oliguria and renal failure
-circulatory failure and shock
the prognosis and treatment is highly variable and depends on the
underlying disorder- administration of either aggressive anticoagulants, such
as heparin and antithrombin
-or coagulants usually in the form of fresh-frozen plasma