wk 12, lec 2 Flashcards
what is the main cause of babeosiosis
babesia microti
what is babesiosis
- Parasitic infection from protozoa babesia from small rodents
o Babesia microti
most common way to get babesiosis and risk factors
- Tick bite; US summer
o Risks: if older, asplenia and immunosuppressed
where does the babesia microti invade
- B. microti invades RBCs and alters morphology
o Increases spleen clearance of RBC, splenomegaly, hemolytic anemia
o Systemic inflammation: TNF-alpha and IL-6 (lung symptoms)
symptoms of babesisosis
- Symptoms: fatigue, malaise, fever, chill, sweat, headache, cough, N/V, neck stiff
o Minority are symptomatic
o Severe- hospital- hemolytic anemia, splenomegaly, infarction, respiratory distress, kidney injury, heart failure
diagnosis of babesiosis
microscope blood smear or PCR for B. microti DNA in blood
treat babesiosis
macrolide antibitoics and antiparasite agents
3 diseases of hyper coagulability
- Virchow’s triad and pathological coagulation
- Inherited disorders of the (anti)-coagulation cascade
- Polycythemia vera
2 diseases of hypocoagulability
- Von Willebrand’s disease
- Acquired thrombocytopenias
is Disseminated intravascular coagulation (DIC) hyper or hypo coagulability
both
virchows triad
- Hypercoagulability of blood
- Abnormal blood flow (stasis or turbulent)
- Injury to vessel wall/ endothelium
shear stress in virchows triad: what happens if decrease
- Shear stress (friction of fluid flow) increases NO, prostacyclin and tPA release (vasodilate and prevent clots)
o In decreased shear stress (i.e. stagnant flow or irregular/ narrow blood vessels) there’s less of these factors –> platelet adhesion + coagulation
inherited hyper coagulable conditions
o Protein C or S deficiency
o Antithrombin deficiency
o Prothrombin mutation (excessive activation)
o Factor V Leiden- activated protein C resistance (most common)
what happens in Factor V Leiden- activated protein C resistance (most common)
Factor V is resistant to inactivation by protein C = excess acitivity in final common pathway
Homozygous is bad; fair bit are heterozygous
what are the sign in Factor V Leiden- activated protein C resistance
DVT in legs or pelvis, led edema and pain, clot can travel to lung and cause pulmonary embolism
what does a mutation in prothrombin causing excessive activation increase risk of and what is the mechanism
Increase risk of venous thromboembolism
More conversion of prothrombin to thrombin
2 acquired conditions increasing coagulation
o Anti-phosholipid antibody syndrome (APS)
o Estrogen containing OCP (birth control)
what does o Estrogen containing OCP (birth control) increase
increase FII (prothrombin), FI (fibrinogen), VII, X, XII, VIII
leads to clotting
o Anti-phosholipid antibody syndrome (APS) - what happens?
Antibodies to protein C, S? endothelial damage?
Venous or arterial thrombi
leads to increased clotting
Acquired thrombocytopenia (hypocoagulability) due to
- Due to hypersplenism, destruction of platelet by autoantibodies (drugs, viral, idiopathic), destruction of platelets by excessive intravascular coagulation, pancytopenia (low RBC, WBC, platelets) from myelodysplastic syndromes (blood cell cancer) and leukemia
what is the most common isolated thrombocytopenia?
Immune thrombocytopenia (ITP)
- Most common isolated thrombocytopenia (isolated= no underlying disease or drug)
what happens in adults vs kids in immune thrombocytopenia
- Kids: virus or vaccination; usually resolves
- Adults: chronic and doesn’t resolve
immune thrombocytopenia- what are there no deficiencies in what are there low levels of
- No deficiencies in coagulation factors
- Platelets destroyed in spleen; splenectomy (removal) helps
- Deficit in platelet production (cytotoxic t cells attack megakaryocytes and inadequate TPO)
- Autoantibodies to platelet antigens- GP Ib/IX
- Overactive Th1 and Th17
removal of what can help immune thrombocytopenia
splenectomy
because there are too many platelets getting destroyed in the spleen
features of immune thrombocytopenia
o Mucocutaneous bleeding= purpura and petechia, epistaxis (nose bleed), gingival bleeds
o menorrhagia, prolonged bleeds in surgery, low platelet counts that increase risk of intracranial bleeds, conditions that increase bleeding risk (NSAID, antiplatelet drug, older, high BP)
how to treat immune thrombocytopenia
splenectomy to reduce platelet destruction and glucocorticoids to increase platelet count
most common inherited bleeding disorder?
von willebrand disease
3 types of von willebrand disease
Tyoe 1 vWD Mild, autosomal dominant, vWF deficit
Type 2 vWD Mild- moderate, autosomal dominant,lots of vWF in circulation but doesn’t function effectively
Type 3 vWD Severe, autosomal recessive, severe vWF deficit (looks like thrombocytopenia & hemophilia)
what does vWF do for clotting
- vWF stabilized VII, forms multimers for platelet adhesion to subendothelial matrix (bind GP Ib/IX and GP IIb/IIIa), made in basement membrane of endothelial cells and platelet granules
in von willebrnad disease what are there deficits in
vWF,
- defects in platelet function, but normal platelet count
o mucosal bleeding, bruising, epistaxis, menorrhagia, prolonged bleeds
how to treat von willebrand disease
- treat with vasopressin (casuse vWF release from endothelial cells)
Disseminated intravascular coagulation (DIC) - what happens to get the clotting then the bleeding
- widespread activation of coagulation cascade form microthrombi and subsequent hemorrhage from consumption of clotting factors and platelets
o fibrin and fibrin degradation products are deposited, vessels occluded then loss of fibrin and consumption of platelets lead to hemorrhage (bleed)
what can Disseminated intravascular coagulation (DIC) be secondary to
- secondary disorder to infection, trauma, malignancy, sepsis, burns
symptoms of Disseminated intravascular coagulation (DIC)
dyspnea, cyanosis, respiratory failure, coma, convulsions, oliguria, renal failure, microangiopathic hemolytic anemia
acute vs chronic effects in Disseminated intravascular coagulation (DIC)
o acute= hemorrhage
o chronic= thrombosis
what type of disorder is polycythemia vera
hyper coagulability
- myeloproliferative disorder (too many RBCs, WBCs, platelets)
things that cause polycythemia’s vera
chronic myelogenous leukemia, essential thrombocytosis, myelofibrosis , clonal stem cell disorder
o Other causes: COPD, renal artery stenosis, OSA, chronic pulmonary disease
where is the a mutation in that causes polycythemia’s vera
- Mutation in autoinhibitory region of JAK2 tyrosine kinase
o Part of cascade for EPO and TPO
what is high in polycythemia’s vera
- Asymptomatic high Hb or hematocrit
why is there neurologic symptoms and what are they in polycythemia’s vera
- Neurologic symptoms b/c hyperviscosity
o Headache, vertigo, tinnitus, visual, TIA, hypertension, venous or arterial thrombosis (cardiac, cerebral), DVT, gout (increase uric acid)
key symptoms in polycythemia’s vera
- Erythromelalgia (burning hands and feet and erythema)
- Pruritic after warm shower (mast cell and histamine)
- Plethoric (ruddy complexion, cyanosis)
- Splenomegaly and hepatomegaly
treatment of polycythemai vera
phlebotomy (blood draw) and hydroxyurea (for cancer) to decrease RBC count and thrombotic events
impaired ____ in megaloblastic anemia
DNA synthesis
what are the 2 causes of megaloblastic anemia
b12 and folate deficiencies
what are b12 and folate needed for and therefore their deficiency causes ,megaloblastic anemia
o B12 and folate needed to synthesize thymidine
b12 vs folate deficiency causing megalobakstic anemia
o B12 deficiency: inadequate diet, pernicious anemia, inflammation in ileum, SIBO
o Folate deficiency: inadequate diet, malabsorption, folate antagonist drugs (methotrexate)
symptoms of megaloblastic anemia
o Symptoms of deficiency of b12 and foalte: weakness, fatigue, sore tough, cheilosis
what do RBCs look like in megaloblastic anemia ? what happens to RBC precursors?
- RBCs and precursors are large and oval shaped – marrow looks hypercellular
o Impaired nuclear maturation and cytosol accumulation
o Delay in maturation of blasts
hemolysis in megaloblastic anemia?
mild or absent
platelet and leukocyte count in megaloblastic anemia
lower
diagnosis of megaloblastic anemia
smear of peripheral blood and b12 and folate levels, test for b12 deficiency neuropathy
pernicious anemia cause
autoimmune attack on parietal cells
what do parietal cells do
o which secrete gastric acid and intrinsic factor in stomach and are needed for B12 absorption
what is pernicious anemia associated with
thyroiditis
(autoimmune)
onset and findings in pernciisous anemia
- slow onset anemia, neurological findings (degenerate spine), paresthesia
the absorption of what vitamin is effected in pernciisous anemai
b12
what does pernicious anemia increase risk of
- increased risk of gastric carcinoma if untreated
bc stomach acid affected
treatment of pernicious anemai
- treat: good prognosis with B12 supplementation
cause of folate defieicny anemia
- Decreased intake or increased requirement (i.e. pregnancy, malignancy)
symptoms of folate defieincy anemia
- Same as pernicious anemia symptoms but without neurological symptoms
o Rule out
treatment of folate deficiency anemai
supplement folate DUH!
2 types of autoimmune hemolytic anemias (AIHA)
warm antibody hemolytic anemia
cold agglutinin disease
what is the innocent bystander effect in autoimmune hemolytic anemias (AIHA)
: innocent bystander damage (antibodies directed to a medication or foreign substance attack RBCs b/c molecule get stuck to RBC)
IgG or IgM in warm antibody hemolytic anemia and cold agglutinin disease
warm= igG
cold= igM
temperature in warm antibody hemolytic anemia
Antibody binds at 37 degree Celsius
IgG in warm antibody hemolytic anemia
RBCs removed in liver or spleen by macrophages with Fc receptors- usually IgG
warm antibody hemolytic anemia and cold agglutinin disease- which is extravascular and intravascular hemolysis?
intravascular= cold
extravascular= warm
3 mechanisms of extravascular hemolysis in warm antibody hemolytic anemia
- Phagocytosis
- Fragmentation
- Cytotoxicity (ADCC)
what can warm antibody hemolytic anemia be secondary to
HIV, viral vaccines and esp drugs
cold agglutinin disease temperature
cold agglutinin disease and IgM
cold agglutinin disease is what type of hemolysis and what is activated
Intravascular hemolysis (complement activation)
cold agglutinin disease can be secondary to
Secondary viral infections: EBV, CMV or mycoplasma infection
what test is done to diagnose Autoimmune hemolytic anemias (AIHA) (cold and warm)
direct and indirect Coombs test
what is a positive Coombs test result
positive= RBCs agglutination
direct Coombs test vs indirect
- Direct coomb’s test (direct antiglobulin test)
o Wash patients RBCs and look for remaining antibodies bound to RBCs - Indirect coomb’s test (indirect antiglobulin test)
o Patients plasma and expose to standard RBC sample
o Look for patients antibodies binding RBCs
what could cause low and high RBC counts
Low= anemias of RBC destruction (AIHA), hypoproliferative anemias, hypersplenism
High= high altitudes, chronic hypoxia, polycythemia
what is the preferred lab metric to diagnose anemai
hemoglobin
hematocrit is
% of total blood volume made up by RBCs
what decreased hemoglobin and hematocrit concentration
Hemoglobin and hematocruit [ ] is dereased in fluid resuscitation (i.e. IV dilutes blood)
MCV
Mean corpuscular volume (MCV)
* RBC size
* Divide hematocrit by total RBC count
MCH
Mean corpuscular hemoglobin (MCH)
* Mass of hemoglobin per red cell
RDW
RBC distribution width (RDW)
* Variance in RBC size
what is anisocytosis
- Anisocytosis= higher RDW (RBC distribution width), more variable size of RBCs
what has high and low RDW (RBC distribution width
- IDA has high degree of anisocytosis (variable RBC size)
- Thalassemia has uniform RBC size
total reticulocyte count assesses
Assess RBC production
Reticulocytes are immature RBCs made in bone marrow then go to blood
normal total reticulocyte count
1%
blood loss does what to total reticulocyte count
increases
total reticulocyte count can differentiate
Help differentiate hypoproliferative marrow from compensatory marrow response to anemia
low total reticulocyte count means and causes
Low= impaired RBC production from nutritional deficiencies, bone marrow infiltration, aplastic anemias
Normocytic, normochromic anemia
▪ Early iron deficiency
▪ Anemia of chronic illness/disease (ACD)
▪ Acute blood loss
▪ Aplastic anemia or other types of marrow failure
▪ Hemolytic anemias
Microcytic, hypochromic anemia
▪ Late iron deficiency
▪ Thalassemia
▪ Lead poisoning
▪ Sideroblastic anemia
▪ ACD can also be mildly microcytic, hypochromic
▪ Mnemonic - TAILS
Microcytic, normochromic anemia
▪ Renal disease
Macrocytic, normochromic anemia
Megaloblastic =
* Vitamin B12 or folic acid deficiency
* Chemotherapy
▪ Non-megaloblastic:
* Liver disease, alcohol use
* Hypothyroidism
* Myelodysplastic syndromes
cell size in vitamin b12 of folic acid deficient
microcytic
prothrombin time (PT/inR) vs activated partial thromboplastin time (aPTT)- which for extrinsic and intrinsic pathwy
PT= extrinsic
aptt= intrsinic
factors in prothrombin time (PT/inR) vs activated partial thromboplastin time (aPTT)
pt/inr: o Factors I, II, V, VII, X
aPTT: o Factors I, II, V, VIII, IX, XI, XII
if prothrombin time is prolonged its because of
o Prolonged if deficient (long time to clot)
Liver disease, hereditary, vitamin K deficiency, warfarin, bile duct obstruction, DIC
- Activated partial thromboplastin time (aPTT) is used to monitor
o Monitor heparin therapy
- Activated partial thromboplastin time (aPTT) increases in
DIC, vitamin K deficiency, warfarin, herparin, cirrhosis, congeital clotting deficiencies
D dimers are used to test for
o *Test for disseminated intravascular coagulation (DIC) (elevated)
Not specific though; also elevated in malignancy, liver, pregnancy, DTV, MI etc
d-dimer are
fibrin degradation fragment that is made through fibrinolysis
