Heme/Onc Flashcards
What lab does Vit K/ warfarin affect
Vit K and warfarin act on 2, 7, 9, 10 C, S and because they have 7 affected the increase PT first followed by PTT (factor 2 and 10)
How is warfarin toxicity reversed
reverse warfarin toxicity with FFP
Why is there skin necrosis sometimes with warfarin?
Protein C and S and anticoagulants that can be deficient and lead to paradoxical hypercoagulant state because they deplete first and can no longer break down factor VIII and V
What is unique about apixaban and riveroxaban
XAaban are Xa direct inhibitors (remember that heparin (-aparins/agrobans) are II a) and do not need lab monitoring, use in poor compliance with Warfarin INR patients
What is used in place of Warfarin with poor INR compliance?
Axaban/apixaban 10a direct inhibitors that don’t need PT and PTT monitoring
Diff between thrombolytics (TPA), warfarin, aspirin and IVC filter use?
Warfarin is long term anticoagulation (as are Xa axabans) and TPA is for acute thrombolysis. IVC filters are when refractory to medical treatment or haad a recent bleed and aspirin is not sufficient for DVT/afib anticoagulation
When to use IVC filter
Use IVC filter with C/I to anticoagulation like a recent bleed or refractory to medical therapy thrombosis
How is warfarin reversed
FFP and vitamin K, FFP actutely
What is a classic feature of hemophilia
classic feature of hemophilia is repeated hemarthroses, they bump themselves on corners and get huge joint effusions or purpura disproportionate to force
What is increased in hemophilia for coag studies?
PTT is increased, PT is fine
FIrst step in suspected hemophilia?
DO a mixing study in suspected hemophilia, which will correct it, Then look at specific factors
what is diff between cryoprecipitate and FFP?
cryo = VIII and fibrinogen and FFP = vit K derivatives
Hemophilia type A (VIII) tx?
DDAVP for VIII release from endothelial cells
Most common inherited bleeding disorder?
vWD is AD and most common inherited bleeding disorder
What factor is low in vWF
AD, most common bleeding disorder has low VIII and high PTT and low BT due to low vWF aglgutination
Dx of vWD
Ristocetein agglutination assay
Tx of vWD
DDAVP helps release VIII
What are the causes of hyperhomocysetiein?
deficiency in cystathonine B synthase which uses B6 as a cofactor and B12 which makes it methionine
What is tx of hyperhomocysteine?
B6 and B12 and anticoagulate
how does HIT present sometimes?
HIT may only present with heparin induction then platelet reduction >50% of the normal
What are the two types of HIT
HIT 1 happens first and is non immune and occurs 1-4d after and less severe than HIT2 occuring 5-10d after and is due to antibodies of PF4
how is HIT diagnosed?
Serotonin release asssay and PF4 ab
How is HIT 1 treated
Just due to temporary effect of heparin on plt and they recover just observe
how is HIT2 treated
extreme drop on platelets associated with thrombosis stop all heparin containing products
What is done in HIT2
STOP ANY HEPARIN PRODUCT and start non-immune derivatives like argotraban
HIT1 tx?
Observe, PLT stay above 100K and rebound versus HIT2 when they fall to 50K from platelet consumption and thrombosis
DIC differentiation from liver levels
VIII is made in endothelium and not depressed in liver disease, but it used up in DIC which has high PT, PTT, BT and low fibrinogen and high D-dimer with low platelets
What does smear show in DIC
in DIC smear shows schistocytes
When are shistocytes seen
schistocytes are due to microangiopathic hemolytic anemia from platelet and fribin mesh and are in HUS, TTP and DIC
Does ITP have schitocyte?
NO, ITP has normal RBC morphology, but TTP has shistocytes
what is the physiologic difference between ITP and TTP
TTP is due to ADAMSTS13 mutation which large multimers of wVF soak up platelets and these deposit all over the body. This causes microthrombi that cause systemic symptoms and then destroy RBC as they go through vasculature. This is why TTP has renal s/s, neuro s/s and fever while ITP does not. ITP is due to igG antibody to platelets and causes megakaryocytes to be large, with a normal RBC morphology because there is no fibrin mesh or deposits anywhere to destroy them, it is just IgG mediated disease. Theese patients are often asyx and need a screen for HIV and HCV as there is a high association
What diseases is ITP associated with
ITP is associated with HIV and HCV
How is TTP treated?
Treat TTP with plasma exchange to get rid of the vWF multimers and do NOT transfuse platelets as this makes it worse and puts more platelets to be consumed by multimers and worsens disease
what is CI in TTP?
In TTP , platelet transfusion is CI, just give plasma transfusion acutely
How is ITP treated
Screen for HIV and HCV and then give steroids if plt are below 30K, otherwise not treatment, secdon line is rituximab and splenectomy
Morphology of RBC in ITP?
ITP has normal RBC and large megas
RBC in TTP
Shcistocytes
Tx of TTP
Plasma change and NO plt
Tx of ITP
steroids (immune mediated) if below 30K plt
What is high in anemia of chronic disease?
Everything in anemia of chronic disease is low except for ferritin which is an acute phase reactant
What are the microcytic (common) anemias?
TICS : thal, iron, chronic disease, sideroblastic
What type of anemia is thal
thal is microctyic
what type of anemia is chronic disease
Anemia of chronic disease is microcytic
What type of anemia is sideroblastic?
In sideroblastic anemia, hemoglobins cannot be made so RBCs keep dividing to main concentration, it is microcytic
Why is ferritin normal or high in chronic disease a microcytic anemia
ferritin is normal or high in chronic disease because it is an acute phase reactant
What are the levels of ferritin and iron in thalassemia?
Ferritin is high and iron is high, it needs to store more, TIBC is inverse of iron because more transferrin is bound and is low
Can alcoholism cause macrocytic sideroblastic anemia?
yes, alcohol can cause macrocytic sideroblastic anemia with stippling, even though sideroblastic is usually microcytic
What are two common causes of sideroblastic anemia
Alcohol causes basophilic stippling because it is a mitochondrial poison and prevents hemoglobin synthesis
Alcoholic with basophilic stippling, cause?
Alcohol is a cause of macrocytic anemia that can cause sideroblasts from mitochondrial poinson
What other deficiency can cause sideroblastic anemia other than too much lead or alcohol
B6 deficiency it is cofactor for the first factor in heme synthesis
where does heme synth occur?
Mitochondria where alcohol poisons which is why it causes sideroblasts and macrocytic anemia
MCC of iron def anemia?
Gi blood loss (get scope) if not on NSAIDS
What is MCHC mean
MCHC is if it is hypochromic or not
What lab value represents hypo/hyperchromia?
MCHC is chromia
When MCV and MCHC are low first step?
MCV and MCHC mean microcytic, hypochromic if both low. The first step for microcytic hypochromic anemia is always iron study and CBC
How is anemia of chronic disease treated?
Anemia of chronic disease is treated by treating the underlying disorder – I.e MTX in RA
What is unique about RDW in iron def anemia
In iron def anemia RDW is increased
What disease is characteristically hyperchromic
HIGH MCHC means hyperchromia = spherocytes = hereditary spheroctyosis
What are the levels of MCV, MCHC, Fe, Transferrin sat, ferritin, TIBC in anemia of chornic disease
In anemia of chronic disease, everything is low or normal except ferritin which can be elevated as it is an acute phase reactant and also stores iron in cells which is sequestered
Sideroblastic anemia is microcytic, what is the iron level?
Sideroblastic anemia is microcytic because HEMOGLOBIN cannot be made, iron cannot be inserted so iron is high, which means ferritin is high and TIBC is low because iron is high
MCC of sideroblastic anemia?
Alcohol is the mCC of sideroblastic anemia
What is the iron level in sideroblastic anemia?
Iron is high, ferritin is high, TIBC is low or reduced
Other than liver disease and neuropathy, what else can INH cause
INH interferes with all things B6
Common causes sideroblasts
Lead, alc (MCC), B6 def
What are two huge, odd key syx for tip off of B12 def for macrocytic anemia
Glossitis is associated with b12 deficiency, as is Crohn’s or any gastric resection (stomach = intrinsic factor) ileum = absorption
Who gets B12 def? (diet)
Vegans and vegetarians
What is diff in syx / labs betwee folic and b12?
Folic def do NOT get the neuro syx
A person who is alcoholic has megaloblastic anemia and is started on folic acid. he then gets neuro syx quickly, what happened?
Both folic acid and cobalamin (b12) cause megaloblastic anemia, treating with folic acid when it is due to b12 precipitates neuro syx, once a megaloblastic anemia is diagnosed, MUST figure out which is deficient before starting folate.
What diet gets megalo anemia?
Alcoholics and vegetarians/vegas
What other things cause megaloblastic anemia other than vegetarians, alc?
Chemotherapeutic agents like MTC and pernicious anemia
Who gest pernicious anemia?
Whites with glossitis and neuro syx and other autoimmune disease
Suspect pernicious anemia in who?
Autoimmune disease like vitiligo, thryoid and whites with glossitis
What drugs classically HY cause low folate?
MTX, TMPSMX and phenytoin
Low haptoglobin, high bilirubin, high LDH and schistocytes suggest?
hemolytic anemia, especially microangiopathic
Why do you wait a month before testing for G6PD def after an episode
because the defective cells are hemolysed early and G6PD level will be normal because only normlal cells remain
How is G6pD diagnosed?
1 month with G6PD levels after hemolytic episode
What is seen on smear for G6pD Def
Heinz bodies and bite cells
When are vaccines given before splenectomy
give vaccines for encapsulated several weeks before
After spleen out, what is given for 3-5 years?
There is a risk of sepsis for 30 years after splenectomy and PCN prophylaxis is needed for 3-5 years after a spleen is taken out
How is PNH diagnosed?
PNH is diagnosed with flow cytometry
what is diagnosed with flow cytometry and CD55/59?
PNH is diagnosed by flow cytometry with CD55 and 59
How is PNH treated
Iron and folate and eclazimub
Hemolytic anemia, venous thrombosis and cytopenia, diagnosis how?
Suspect PNH due to CD55/9 anchor defect and complement hemolysis causing thrombosis as well get blood cbc studies and diagnose with flow cytometry
Hey result in HS on blood smear?
MCHC is high (hyperchromic) in HS due to spherocytes
Classic s/s of hereditary spherocytosis
Hemolysis, splenomegaly and jaundice
How is HS treated?
Treated with splenectomy as this RBC removal causes syx and gallstones, but the RBC function fine they are just smaller
Defect IN HS
Spectrin or ankryin
How is HS dx?
Osmotic fragility test when spherocytes are on smear
How is HS inherited?
HS is autosomal dominant
When should you suspect HS in a family history?
HS often has gallstones at a young age from the hemolysis and spilling of bilirubin, it is AD and this will be seen in family members
HS labs?
Commonly have gallstones, but high MCHC is the key one, along with high RDW (don’t confuse with iron def anemia) and dx with osmotic fragility or esoin 5 malemide test
What has spherocytes, high MCHC AND high RDW?
HIGH MCHC and RDW = HS (AD disease)
What do all SCA patients need?
SCA patients commonly get macrocytosis from constant bone marrow turnover due to normocytic hemolytic anemia. They need folate supplementation
What anemia is seen in SCA
SCA get both normocytic hemolytic (sickling) and macrocytic (constant bone marrow turnover) anemia, so they all need chronic folic acid supplementation due to this chronic folate def from proper bone marrow response
How is SCA inhertied?
SCA is inherited AR
MCC presentation of AR SCA?
AR (it is AR because there are CARRIERS) is dactylitis
Why do so many people with SCA have nocturia, and is it trait only or full disease?
SCA patients, trait and full-disease have nocturia (hypothenuria) because sickling in kidney vasa recta disallows urine concentration
What is seen on SCA smear?
Sickling is NOT ALWAYS PRESENT, but almost all have Howll-Jowell bodies from splenic autoinfarction
Best diagnostic test for SCA?
Hg electrophoresis
Why is hg electrophoresis best test for SCA?
SCA the cells are not always sickling if not hypoxia/stressed/at altitude = do electrophoresis in a family with history of it
How is AIHA diagnosed (both types_
Both types of AIHA is diagnosed with Coombs testing
what are warm IgG AIHA?
Dx with coombs and is SLE, CLL and drugs and treat with steroids
How is warm IgG AIHA (sle, CLL, drugs) treated?
Steroids
How is cold IgM (Myco and Mono; M= IgM) treated?
Avoid cold and ritixumab if severe
What are s/s of aplastic anemia?
Aplastic anemia is pancytopenia with pallor, eakness, infection, petechiae, bruising and bleeding
How is aplastic anemia diagnosed?
CBC then bone marrow biospy with fatty, hypocelluar type
How does B thal minor usually prsent?
It usually presents as iron def anemia and is confused with it, note RDW and RBCs are different from iron
Does B thal minor need tx?
NO. just observe
What is a common presenting syx of PCV
PCV commonly presents as HTN
What is noted on labs in PCV
High Hct often >60%, but other cell lines are elevated as well
What causes PCV
JAK2 mutation, hypoxemia (Chronic) or low volume
What does a low EPO with high Hct tell you
PCV due to Jak2 mutation
How is PCV treated?
PCV is treated with phlebotomy to hct
s/s of tumor lysis syndrome
GERD, Histamine, AKI, gout
Does PCV need EPO? what causes the overproductio?
PCV (if JAK2) is EPO INDEPENDENT due to Jak2 mutation and self proliferation
PCV often presents as just HTN, is it reversible?
Yes, it is reversible with phlebotomy.
What are classic s/s of porphyria
Vesicles, hyperpigmentation, abd pain and urine color changes after alc, barbs or OCP
what disease is cutanea tarde associated with
It is associated with HCV
How is porphyria treated in hcv?
IFNa if they have HCV
How is porphyria treated chronically
Hydroxyurea to increase HbF
How is porphyria diagnosed
CBC and smear followed by urine or palsma porphyrin levels
What can provide relief during acute porphyria attack
Glucose which prevents more photoprophryin from being made
Someone Immediately has issues after blood transfusion, cause?
igA def
IgA def causes issues with transfusion when
IgA causes transfusion issues immediately with wheeze, tachy and increased RR and urticaria
How is IgA def transfusion issue treated?
IM epi, steroids and histamine block, happens immediately with drip
When does febrile hemolytic occur
1 hour with flank pain, hemoglobinuria, DIC and renal failure
Febrile hemolytic reaction due to
ABO mismatch, 1 hour after, flank pain, hemoglobinuira, DIC, renal failure + coombs and pink plasma
Nonfebrile hemolytic reaction is d/t and happens when?
Cytokines. 1-6 hours, fever and chills only
Amanestric blood reaction is d/t and happens when?
2-10d after, Rh factors, minor reaction.
Anaphylactic shock from PRBC is due to
igA autoantibodies in IgA deficient individual = AnAphlActic - IgA deficient
When are PRBC given
Hg less than 7 (even if active bleed) or Hg
RIsks in acute ABO hemolytic reaction
Happens within an hour and get AKI and DIC, may bleed from IV site
What are the AE of mycophenolate
bone mycow suppression
AE of azathioprine
Azathioprine is a 6mp analog causing leukopenia, dose related diarrhea and hepatotoxicity
AE of cyclosporin
Most serious is renal toxicity causing HTN and hyperkalemia from renovascular constriction and gum hypertrophy and hirsutism along with neurotoxicity and tremor
AE of tacrolimus
both cyclosporin and tacrolimus are IL2 calcinuerin inhibitor and cause renal toxicity and hyperkalemia with neurotoxicity and HTN, but only cyclo cause hirsutism and gum hypertrophy
AML has risk of what presentation
AML causes DIC due to Auer rods
What is seen on smear with AML
AML has Auer Rods
What is the defect in AML
AML is due to retinoic Acid receptor rAr and causes degran of auer rods and DIC
how is AML treated?
Treat AML with retinoic acid all trans
Other than rods and DIC and rAr issue (vitamin A) wha tis seen in AML smear
Myeloblasts
How are the leukemias diagnosed
CBC with smear and then flow cytometry/genetic analysis
Who gest CLL
CLL is OLDER adults
What are two markers for CLL
smudge cells and CD5
what has worse prognosis for CLL
thrombotycopenia has worse prognosis
How is CLL staged
Prognosis based on syx, anemia to thrombotycotpneia is the worse
Who has Phila chromosome?
CML is Phila crhomosome
What is defect d/t Phila Csome?
Defect due to Phil Csome is ABR Tyr kinase
How is CML treated
9;22 ABR tyr Kinase with imatanib
CML s/s
CML classically has low LAP and basophilia withi granulocytes in all stages
Where do you see granulocytes in all stages with ABR Tyr Kinase mutation and 9;22 treated with imitanib and basophilia?
CML = basohpils, granulocytes, 9;22 phila, imabitninb, tyr kinase, LAP low is classic
How is hairy cell treated?
Hairy cell is cladribine and and imitanib is CML and retinoic acid is AML
What disease are assoc with NHL
NHL is due to HIV and autommine commonly and many nodes non contiguously are invovled
What are the s/s of HL
HL is a group of contiguous nodes
What is asso with HL?
HL is assoc with EBC and Reed-sternberg CD15 and 30 cells with owl eye nuclei
HL distribution and association
EBV for HL vs HIV /autoimmune for NHL
When do you see alcohol induced pain and LAD?
Alc induced pain is a rare association for HL which is REedSternberg and EBC associatied
What is the best first test for suspected MM
For suspected MM you get serum protein elctrophoresis
What presets with high calcium, renal failure, anemia and bone pain?
MM
Best test for MM?
Initial, Electrophoresis looking for M spike fo IgG then Bone marrow test with >10% plasma cells
What is MGUS
MGUS is IgG related prolfieration without CRAB findings
What are urine s/s of MM and Smear s/s
Rouleaux formation and Bence Jones protein
What are classic s/s of MM
M/m is IgG related and causes CRAB of calcemia, renal, anemia and bone with 10% blasts in bone marrow confirmed after igG M SPike
What lesions are seen on MM bone scan
MM is an osteoclastic process
What is the path diff in MM, MGUS and Waldenstrom
MM = 10% plasma cells and IgG MGUS = less than 10% plasma cells in marrow and IgG and no CRAB syx Wald = IgM and hyperviscosity, elderly, enroged eye vessels, organomegaly and pain in arms/legs -- BMP shows Dutcher bodies that are PAS + IgM deposits and Raynaud common
MGUS s/s
Raynaud, organomegaly, eye engorgement, extremity pain, neuro disorders
walden dx
IgM - M spike with Dutcher, PAS + IgM bodies
When do you IgM M spike with Dutcher PAS + bodies?
Waldenstrom
What is another way to distinguish MM from MGUS?
BONE XRAY shows lytic leasions in MM (cannot do bone scan which only shows blastic lesions)
Amyloidosis most commonly affecst
Kidney, heart and liver affected by amyloidosis
S/s of amyloidosis?
Kidney, heart, liver and skin/organomegaly and sometimes neural function. Restrictive cardiomyopathy, waxy skin and big tongue and organs, proteinuria and elevated LFTs with heart dysfunction (Restrictive) normal cavity size
How is amyloidosis dx?
fat pad biospy
Gold standard for HIT testing?
Serotonin release assay
HOw does HIT II present
5-10 with 50% decrease in platelets and DIC/clotting; stop heparin and give argotraban derivative
How is warm AIHA treated?
Warm AIHA is due to IgG and treated with steroids versus cold IgM AIHA treated with avoiding cold and ritixumab if refractory
What inherited anemia has high MHCH (hyperchromic) and high RDW?
Hereditary spherocytosis = MCHC high and high RDW with family history/ or early gall stones
What does INH interfere with (vitamin)
INH / TB tx interferes with B6 = sideroblastic anemia = peripheral neuropathy = hepatotoxic = homocysteine increases
CML smear
Extreme leukocytosis >100K, lots of granulocytes/barely mature neutrophils and 9;22 CML Phil Csome and treat with imatinib + basophilia
Classic cell elevation in CML
basophilia
TTP smear?
TTP smear has schistocytes (TTP, DIC, HUS, microangiopathic)
S/s of TTp
TTP cause neuro changes, renal failure, thrombocytopenia with shistocytes on peripheral smear and is associated with HIV
