Pathology-rbc And Bleeding Disorders Flashcards
Red cell indeces:
Average content/mass of hemoglobin per red cell
Mean cell hemoglobin
Mean cell volume- ave volume of rbc
Mean cell hemoglobin conc- average hgb in given volume of rbc
Red cell variation of red cell volume- coeeficient variation of rbc volume
average hgb in given volume of rbc
Mean cell hemoglobin conc
Mean cell hemoglobin- ave volume if red cell expressed in femto litters
Mean cell volume- ave volume of rbc
Red cell variation of red cell volume- coeeficient variation of rbc volume
Site of hemolysis with:
Anemia
Jaundice
Splenomegally
Extravascular. Main feature is splenomegally bec if sequestration
Intravascular main feature is increased direct bilirubin manifested as jaundice. Other presentations: hemoglobinemia, hemoglubinuria amd hemosiderinuria
What is the expected peripheral smear in hemolytic anemias
Normocytic normochromic
Primary myelofibrosis also presents with normocytic normochro,ic anemia. It’ fibrotic obliteration of bone marrow spaces
Types of hemolytic anemia
Hereditary spherocytosis G6pd deficiency Sickle cell Thalasemia Autoimmune ha Microangiopatjic ha Macroangiopathic ha
Autosomal dominant
Ankyrin and spectrin mutation causing structural changes of rbc
Rbc lacks central pallor
Splenomegally
Hereditary spherocytosis
Spherocytes- rbc lacks pallor
Aplastic crisis is associated with what virus?
Parvo virus
Hemolytic crisis is assoc with EBV mononucleosis
Small dark nuclear remnants in rbc in ASPLENIC patients
Howell-jolly bodies seen in heredetary spherocytosis
Other assoc sx: aplastic crisis (parvo virusb19) and hemolytic crisis (EBV)
X linked recessive
EPISODIC hemolysis triggered usually by infection
Other triggers (antimalarials, sulfonamides. Fava beans)
Protective against what disease?
Malaria
Dx at point: g6pd deficinecy
Reduces nadph to nadph which acts as reducing agents for oxidized rbcs
Recovery phase for hemolysis is heralded by reticulocytosis
Membrane bound precipitates on denatured globin chains. These can be phagocytized by macrophages leaving a distinct bite in rbc (bite cells)
Heinz bodies seen in g6pd deficiency
Bite cells not appreciated in asplenic patients
Point mutation in 6th codon affecting the BETA GLOBIN
Replacement of glutamate with valine
Autosomal recessive
Autosplenectomy
Sickle cell anemia
target cells, reticulocytosis, sickle cell, howell jolly bodies (seen also in spherocytosis)
Target cells or codocytes are dehydrated rbc with bulls eye appearance
Why is sickle cell in infants asymptomatic until 2-4months of age?
Due to high amount of fetal hbg (2alpha, 2gamma)
Adult hbg is 2alpha:2beta
Sickle cell affects only beta globins
Sickle cell crisis (three tyoes)
Vasoocclusive: dactylitis
Sequestration: splenic enlargement
Aplastic crisis: parvo virus b19 (seen also in spherocytosis)
Aplastic crisis caused by parvovirus b19 is seen in which condition
Heredetary spherocytosis
Sicle cell anemia
What is the drug of choice fo sickle cell anemia? And moa?
Hydroxyurea. It increases fetal hemoglobin
Tyoes of alpha thalasemia
Silent carrier state: deletion of ONE alpha globin chain
Alpha thalasemia trait: TWO globin chains
Hemoglobin h bonding disease- THREe
hydrops fetalis-all four alpha globin
Tetramers of gamma-globin chains sen in hydrops fetalis thalasemia
Hb barts
Types of beta thalasemia
Cooley’s anemia or Beta thalasemia major
BT untermediate
BT minor
Dehydrated rbc with bulls eye appearance is seen in what conditions
Thalasemia
Sickle cell anemia
These are called codocytes ir target cells
Codocytes basophilic stripling Anisocytosis Poikilocytosis Microcytic, hypochromic anemia Chipmunk facies Crew cut appearance if skull
Thalasemia
Small peripheral dots in rbc with microcytic hypochromic anemia is seen these conditions:
TAIL: thalasemia, anemia of chronic cause, ida, lead poisoning
The dots are called basophilic stippling
Treatment of hemochromatosis? If unresponsive, what pharmacologic agent, what moa?
Phlebotomy
Deferoxamine via chelation
Increcreased compliment mediated rbc lysis c5b-ca
Decreased cd59 expression
!Hemoglobinuria upon waking up
Thrombosis (mcc of fatality)
Paroxysmal nocturnal hemoglobinuria
Warm agglutinin is mediated by what immuno globulins?
IgG in warm aglutinin autohemolyric anemia
Also seen in methyldopa, sle and cll hemolysis
Another kind is cold mediated autohemolytic anemia, igM mediated seen in Mycoplasma and Mononucleosis
“Cold ice cream is mmm”
Coobs tests that checks patient’s serum for anti rbc surface iG
Indirect coombs test
Direct coombs test checks if patients rbs is coated with igG
Damage if rbc thriugh narrowed or obstructed lumina
Usually with cardiac valve prostheiss
Microangiopathic hemolytic anemia
Schistocytes are fragmented rbc, called helmet cells if cut in half
Burr cells or echinocytes are rbcs with spikes
What condition?
Rbc trauma
Hepatosplenomegally is seen in which conditions?
These are the extravascular site of hemolysis:
Heredetary sphenocytosis
Sickle cell anemia
Thalasemia
G6pd is an exemption bec site depends on presence of assaulting factor
Conditions with hemolytic anemia caused by external factors ex drugs, temp
Autoimmune hemolytic anemia
Microangiopathic hemolysis
Macroangiopathic hemolysis
Intrinsic hemolysis- Conditions with hemolytic anemia caused by inherent structural defect
Anemias from diminished erythropoeisis
Megaloblastic anemia Pernicious anemia Iron defeciency anemia Anemia of chronic disease Aplastic anemia Pure cell aplasia
Macroovacytes (big oval rbcs)
Hypersegmented neutrophils
Has neurologic symptom
Causes are:
Impairment if dna synthesis leading to ineeficient vit b12 deficiency
Deficiency of nutrients
Megaloblastic anemia sec to vit b12 deficiency
Folate acid defficiency has no neurologic symptoms
What parassite is assoc with vit b12 deficiency? Treatment.
Diphyllobotrium latum from raw fish (flatworm)
Treat with praziquantel
“PRESSiquantel- flats the worm”
Megaloblastic Anemia Atrophy of the fundic glands of stomach Intestinalization (with goblet cell formation) Atrophic glossitis (glazed beefy tongue) Autoimmune attacking the parietal cells
Pernicious anemia
Parietal cells produces intrinsic factor for vit b12 absorption
Chief cell- zymigen cells- producing pepsiongen
Test for differentiating megaloblastic anemia with vit b12 deficiency?
Schiling test
Stage 1: oral or im vit b12
Stage 2: intrinsic factor
Normal 1 normal 2- deficiency
Low 1 normal 2- pernicious anemia
Low 1 and 2 malabsorption
Most common nutritional disorder in the world? Microcytic hypochromic anemia Basophilic stripping Spoon nails (koilonychia) Pica
Iron defficiency syndrome
Other basophilic stripping and microcytic and hypochromic conditions: “TAIL”
What parasitic infection causes ida? Treatment
.
Hookworms (necator, ancylostoma) -blood suckers
Albendazole
Plummer vinson syndrome. What maliganancy should be ruled out?
Ida
Esophageal webs
Atrophic glossitis
Inc risk of developing colorectal scca in the elderly
Ida in the elderly should be checked for colorectal ca.
Most common cause if anemia among hospitalized patients
Increase in il-6 –>hepcidin
Anemia of chronic disease
Inhibits ferriporin function of macrophage reducing transfer of iron frim storage to bone for erythropoeisis
Hepcidin
Stimulated by il-6 in anemia of chronic disease
PANCYTOPENIA
Hypocellular bone marrow with fat cells
Absent splenomegaly
Reticulocytopenia
Aplastic anemia
Vs. myelodysplastic syndrome–> the bine marrow in mds is hypercellular
Drug known to cause aplastic anemia? Chemical to cause aplastic anemia?
Chloramphenicol
Benzene
Selective hypoplasm of erythroid elements?
Thymoma with leukemia (paraneoplastic syndrome)
Differentiate with aplAstic anemia
Pure red cell aplasia
Anaplastic anemia is PANCYTOPENIA
Causes of Bleeding disorders
Increased vessel fragility
Platelet deficiency
Platelet dysfunction
Derangement of coagulation
NORMAL bleeding parameters
Non thrombocytic purpura
Seen in scurvy
What caused the bleeding disorder?
Increased fragility of vessels
Spontaneous bleeding happen in what platelet level?
20,000/ml
Platelet transfusioon threshold
Thrombocytopenia is defined as?
Antiplatelet antibodies
Megathrombocytes
Spleen congestion
What treatment?
Case point: immune thrombocytopenic purpura
Most feared complication: ich
Tx with glucocorticoids, splenectomy, immunoglobulin or
rituximab (anti cd20 antibody)- if there is relapse s/p splenectomy
Thrombotic Thrombocytopenic purpura pentad vs hemolytic uremic syndrome triad?
Fever and neurologic deficits in TTP
Common sdx: thrombocytopenia, microangiopathic hemolytic anemia, renal failure
Ttp caused by deficiency of ADAMTS13 vWf metalloprotease
HUS by shiga like toxin EHEC 157:7 from burger
Increased bleeding time
Decreased GP1b leading to defective adhesion
Decreased platelet count
Bernard soulier syndrome of platelet dysfunction
Increased bleeding time
Decreased GpIIb-IIIa
Defective platelet to platelet aggregation
NORMAL platelet count
Glanzmann’s thrombasthenia
Three Types of coagulation disorders
Von willebramd disease
Hemophilia
Disseminated intravascular coagulation
Most common inherited bleeding disorder
Differentiated from bernard soulier sundrome for having normal platelet count
What is the treatment?
Desmopressin and comc factor 8 and vWf
Dx at point: von willebrand factor disease. VWf is associated with factor 8. Without it f8 decreases
Most common heredetary disease associated with life-threatening bleeding
What is the treatment?
Factor 8 and cryoprecipitate
Case: hemophilia A
“A, eight”
Also known as christmas factor. Deficient in what coagulation disorder?
Hemophilia B, factor 9
“9 benign (less life threatening bleeding)
Consumptive coagulopathy Thrombohemorrhagic disorder (coexistent state)
Dissiminated intravascular dissemination
Common factors with ultimate goal to activate f2
10, 2, 5 fibrin
Extrinsic factors
7
With common factors 10 2 5 fibrin
Prothrombine time tests for
Extrinsic + common factor
Bleeding time- speed platelet plug is formed.
Partial thromboplastic time- intrinsic+common factor
Causes of DIC
STOP Making New Thrombi
Sepsis (gram neg) Trauma Obstetric complications (abruptio placenta) Pancreatitis Malignancy Nephrotic syndrome Transfusion
Important in diagnosing dic?
D dimer most specific
Other ddx: Fibrinogen Platelet count Pt/ptt Fibrin degredAtion products
DIC
Fibrin thrombi leading to massive adrenal hemorrhage.
Renal Complication of meningococcemia and N. meningitidis
Waterhouse-friderichsen syndrome
Dic special situation
Sheehan syndrome: post partum pituitary necrosis
Waterhouse friderichsen sdx
Toxemiaof pregnancy
Overall most common cause of anemia?
Bleeding
Ida is most common anemia of defeciency
