USMLE PATHOLOGY - Haematology
What type of anemias are TTP (Thrombotic thrombocytopenic purpura ) and HUS (hemolytic uremic syndrome)? Can you tell the difference between the 2 in terms of presentation?
- Both Are microangiopathic haemolytic anemias (MAHA) - which are non-immune type. - So both have anemia and thrombocytopenia AND fever. - TTP is mainly seen in ADULTS and have mainly CNS features - HUS is mainly seen in KIDS with renal failure and milder CNS features. - Both have normal PT and APTT, fibrinogen = unlike DIC (prolonged pt, apt and low fibrinogen and incr fribirn degradation products). - These pt - DO NOT BLEED (unlike DIC)
Q 19 A 32-year-old Caucasian woman experiences three episodes of deep venous thrombosis in a six-year period. She has a history of pulmonary embolism as well. The patient's partial thromboplastin time (PH aka APTT) is within normal limits, and remains unchanged when activated protein C is added to her plasma. The most likely cause of this patient's problem is:
- INHERITED -> FACTOR 5 LEIDEN MUTATION - Consider it in young (<50yo) with recurrent DVTs and absence of obv explanatons - They are resistant to anti-thrombotic effects of activated protein C (activated protein C resistance) meaning that there is mutation in factor 5.
in vWD disease which lab finding is elevated?
- Increased APTT (measures intrinsic pathway) is elevated = due to F8 deficiency (cos vWF carries f8 - which is needed for f10 and thrombin). -Remember it is a bleeding disorder
Q17: A 26-year-old Caucasian female is found to have a single amino acid substitution (glutamine for arginine) near the protein C cleavage site in her coagulation factor V gene product. The patient is at greatest risk for developing which of the following conditions?
- PULM THROMBOEMBOLISM - This pt has FACTOR V LEIDEN (ie a variant of F5 which leads to hypecoag cos here the mutation in protein C (natural anticoag) cannot inactivate F5 anymore-> so more factor 5 leiden leads to incr thrombin production. In addition there is lower anticoag cos of mutated protein C -remember that normally F5 (is activated by thrombin) and then it activated F10 to create more thrombin. BUT normally F5 is inactivated by Protein C. - So factor 5 leiden -> incr coag and decr anticoag -> hypercoagul (thrombophilia). - So are more likely to develop: -DVT -> pulm embolisms -Cerebral vein thrombosis -Recurrent pregnancy loss. - Heterz carriers (1-9% of Caucasian in world) of factor 5 leiden -> 5-10x incr risk of thrombosis while homoz is 50-100x.
What is ITP?
- idiopathic thrombocytopenic purpura aka "immunopathic" thrombocytopenia - mainly see thrombocytopenia - immunopathic cos thrombocytopenia is due to ab against platelets and ab form complexes - which stick together - so uncommon spont bleeding!! Ie do nt bleed - PT and APTT are normal
when does Hereditary deficiency of GP lIb-Illa receptors occur? ie whats the disease called? - what do you see? - is platelet aggregation normal to adp or ristocetin?
- occurs in Glanzmann thrombasthenia. (defic of GPIIb/IIIa which normally allow platelet aggreg) - with mucocutaneous bleeding and increased bleeding time - Platelet aggregation in response to ristocetin (which is helps to activate the rec) is normal, but is decreased with addition of ADP (opposite to vWF deficiency/disease).
What are the 3 main differences between DIC and TTP-HUS (MAHAs)
-DIC: Pt BLEED PT and APTT are PROLONGED Fibrinogen is LOW (hence lower fibrin so less clots ie bleed more). Fibrin degradation products (d-dimer) are INCREASED - TTP-HUS Pt DO NO BLEED PT and APTT - normal Fibrinogen = Normal.
Q99 55yo male -has fatigue and exertional sob - dx with macrocytic anemia. - endoscopy shows atrophic gastritis - CYANOCOBALAMIN is started as tx. - what blood parameter first increases and then decreases (bell curve)?
-RETICULOCYTE COUNT does that. - tx for macrocytic anemia (vitb12 def) is cyanocobalamin (vitb12) - the pt had atrophic gastritis -> vit b12 def and also hypochlorhydria, decr IF production, megaloblastic anemia, INCR gastrin and methylmalonic acid (MMA) and homocysteine levels. - so once the vitb12 tx is started -> the rate of erythropoiesis incr so there is release of immature reticulocytes from bone marrow into bloods -> reticulocyte count incr within a weeks while the anemia is corrected over 6wks (ie incr in Hb levels)
What type of anemia is Paroxysmal nocturnal haemoglobinuria (PNH)? And what 2 features does it have?
-it is a complement activated haemolytic anemia -associated with thrombocytopenia and leukopenia
1. Give an example of IMMUNE cause of hypercoagulability? 2. Give an example of DIETARY cause of hypercoagulability? 3. Give an example of INFECTIOUS cause of hypercoagulability? 4. Give an example of NEOPLASTIC cause of hypercoagulability? 5. Give an example of INHERITED cause of hypercoagulability?
1. ANTIPHOSPHOLIPID ANTIBODY SYNDROME -> hypercoagula. But will have prolonged APTT eg lupus anticoagulants. 2. FOLIC ACID DEF -> hyperhomocysteinamia = leads to thromnbosis by degrading arterial structures like collagen and elastin. 3. ENDOVASCULAR INFECTIONS and systemic inflame states. 4. Eg ADENOCARCINOMA OF LUNGS, PANCREAS AND COLON. By releasing of pro-coagulants tumour products. Also have vascular stasis due to blood flow obstruction from tumour. 5. FACTOR 5 LEIDEN MUTATION - Due to resistance to inactivation by protein C. -> DVTs in young pt.
someone monoz with HbSS - what would you see in findings?
1. INCR MCHC 2. incr reticulocytes count ALSO see howell-jolly bodies. HbSS when >80% of HbS and the rest is HbA.
Q42. A 56-year-old male is being evaluated for increased fatigability. His past medical history is significant for - severe aortic stenosis that required - aortic valve replacement, - diabetes mellitus, and -osteoarthritis. - Peripheral blood smear findings are shown on the slide below (shows fragmented rbc) what are the 5 main lab findings?
1. LOW HAPTOGLOBIN 2. haemoglobinemia (free hb in serum) 3. haemoglobinuria (free hb in urine) 4. INCR serum LACTASE DH. 5. INCR serum INDIRECT BILIRUBIN (Cos of heam and porphyrin breakdown) - the mechanical aortic valve causes rbc to hemolyse and are seen in film as fragmented rbc called SCHISTOCYTES aka HELMET CELLS. (Also seen in MAHAs like dic, hus) - the INTRAVASCULAR destruction of rbc causes free hb in blood and urine. - NORMALLY the FREE Hb binds to HAPTOGLOBIN which promotes hb excretion by the reticulo-endothelial system (aka spleen and lymph nodes where there is macrophages) -HOWEVER with intravascular hemolysis -> there is xs of Free Hb so exceeds binding capacity of haptoglobin which thus DECR in level!!
1.what p/c would you see in Anti-thrombin III Def? 2.give an eg of autoimmune phenomena with bruising?
1. anti-thrombin III def -> VENOUS THROMBOSIS and HYPERCOAGUL state. 2. HEPARIN-INDUCED thrombocytoPENIA (HIT) -> autoimmune condition that would lead ton bruising.
the absence of what finding is key for dx aplastic anemia?
ABSENCE OF SPLENOMEGALY - needed to dx aplastic anemia cos means that problem is not in periphery but in bone marrow
Q80. 41yo female - low grade fever - pallor - easy fatigue - see an unusual protein in her WBC which shows affinity for VIT-A derivatives. most likely dx?
ACUTE PRO-MYELOCYTIC LEUKEMIA (APL) type 3 part of AML!! - where wbc produce aberrant protein with affinity for RETINOIC ACID - APL happens due to t(15,17) mutation where there is a transfer of the gene that codes for retinoid acid rec (RAR) and forms a new gene called PML/RAR - normally RAR plays a role in proper differentiation of myeloid precursors and allow maturation. - but in t(15,17) mut => abn retinoid acid rec (rar) and unable to allow myeloid precursor to differentiate. TX with ALL-TRANS-RETINOIC ACID (ATRA) - stimulates diff of myeloblasts into mature granulocytes - allowing 90% remission of APL.
in CML and some ALL what genetic rearrangement do you see?
BCR-ABL rearrangement/fusion due to translocation of 9,22 (t9,22) =PHILADELPHIA chromosome. which increases tyrosine kinase activity. B Cell rec. = bcr.
Q168. 56yo - fatigue and occasional palpitations over 6months - a lo of stress - drinking 2-3 beer cans on weekends - Hb is 8.5 g/dl - peripheral blood smears shows pale microcytes - what should the initial evaluation of this pt be?
BLOOD LOSS -this pt has microcytic and hypochromic (pale) anemia which is mainly due to Fe def. - main and most dangerous mechanism of fe def is blood loss. - women of childbearing age (not here) are fe def due to menstruation - so adult males and post-menop women should be assessed if low Hb. - to rule out any malignancies in GI (by endo and colono -scopies) - fatigue and palpitations are common features of anemias NB - anemia of chronic liver disease is usually normocytic or slighly macrocytic and see TARGET CELLS in smear. (bulls-eyes)
Q.43 4yo male boy - dies from overwhelming infection - autopsy showed - bone deformity - hepatosplenomeg - clumps of erythroid precursor cells in liver and spleen - these precursor presence is related to what dx?
CHRONIC HEMOLYSIS - presence of erythroid PRECURSORS -> in liver and spleen -> means EXTRAMEDULLARY HEMATOPOIESIS - this is stimulated by erythropoietin and a hyperplastic marrow cell invasion of extramedullar organs - EXTRAMEDULL heamatopoiesis is mostly caused by severe CHRONIC HEMOLYTIC ANEMIA - eg BETA THALASSEMIA. - splenomegaly cos of hemolysis in there - skeletelal abn like maxillary overgrowth, frontal bossing (chipmunk facies)., pathological fractures, thins the bony cortex and impairs bone growth. its not due to erythropoeitin def (in CKD) -> would see anemia and not extramedull hematopoiesis.
Q68. 30yo female - sudden abd pain - ascites - anemia - reticulocytosis - leukopenia - thrombocytopenia - hepatic vein thrombosis - flow cytometry shows deficiency of CD55,59. what is the cause of her anemia?
COMPLEMENT ACTIVATION - ie this is PNH (PAROXYSMAL NOCTURNAL HEMOGLOBINURIA) - dx when there is triad of anemia, thrombosis, pancytopenia. - it is not paroxysmal nor nocturnal. - due to PIG-A gene mut - normally rbc have receptors that bind to CD55,59 which prevent complement attachment so -> do not hemolysis. - however in PNH there is def of CD55,59 so now complement attach to rbc -> hemolysis. - - with PNH get thrombosis (of hepatic vein often and budd chiari syndrome) - def of cd55,59 is DX of PNH
Q60. 54yo - with megaloblastic anemia - ataxia - given radiolabelled COLABAMIN (vit b12) -> by mouth followed by a Unlabaled IM injection of cobalamin - urine radioactivity is Normal most likely cause of pt symptoms?
DIETARY COLABAMIN (VIT B12) DEFICIENCY - this is the SCHILLING TEST - used to differentiate DIETARY (problem of intake) vs MALABSORPTION and PERNICIOUS ANEMIA (problem of gut abs) - in DIETARY one the ORAL RADIOLABELED vit b12 is abs normally in gut and excreted normal in urine (like HERE) - while in malabsorption and pernicious anemia -> oral radiolabeled vitb12 would not be abs in gut and not seen in urine but IM injection would work normally cos bypass gut.
Q12. A 50-year-old female with a history of - systemic lupus erythematosus is admitted with - fever, chills, and burning on urination. - She quickly becomes hypotensive despite aggressive resuscitation. -Urine and blood cultures grow gram-negative rods. -One hour after admission, she starts bleeding from venipuncture sites. -Laboratory studies show the following: - low platelets - high PT and partial thrombloplastin time (APTT) most likely diagnosis?
DISSEMINATED INTRAVASCULAR COAGULATION =DIC formation of blood clots in the small blood vessels throughout the body BUT the coagulation process consumes clotting factors and platelets, normal clotting is disrupted and severe bleeding can occur from various sites. - pt has UTI which results in septicemia -> shown by positive urine and blood cultures with gram neg rods. - DIC is a common complication associated with sepsis. - occurs due to intro of factors that start intravascular thrombosis. - suspect DIC if see: - sick pt - both high PT and APTT - low platelets - high fibrin degradation products like D-dimer - low fibrinogen - pt is bleeding.
which drug tx is linked to Deficiency of thromboxane A2 ?
Deficiency of thromboxane A2 is associated with ASPIRIN treatment, - due to irreversible inactivation of COX in platelets. - The result is decreased platelet adhesion and aggregation
Q110 25yo black female - has skin rash and arthralgia - has low range proteinuria and abn urinary sediment. - renal biopsy confirms focal proliferative glomerulonephritis. - blood results shows LOW rbc, wbc and platelets. what is the cause of these findings?
Dx = SLE cos of skin rash and arthralgia and black woman. - Haem shows -> PERIPHERAL DESTRUCTION OF BLOOD CELLS. -in fact haem abn (like pancytopenia) are common in SLE. -> due to formation of Ab against blood cells. = aka type 2 hypersensitiviy. -anemia -> is an autoimmune hemolysis = see spherocytes, +Ve Coomb test and extrabv hemolysis. - the SLE-associated thrombocytopenia = like ITP ie due to ab against platelets which are destroyed. - low wbc (neutropenia) is less common. NB - this is not ineffective hematopoiesis cos here the blood cells are broken in bone marrow and eg are thalassemia and myelodysplastic syndrome - this is not bone marrow hypo/aplasia cos it is due to exposure to toxins like anti-metabolites and chloramphenicol. - this is not dilutional pancytopenia cos this happens after massive rbc transfusion.
Q180. 20yo male - recurrent jaundice - no recent travel or pmh - unprotected sex with multiple partners - normal bp, pulse etc - has pallor icterus - mild splenomegaly - no lymphadenopathy nor hepatomeg - lab shows: hb 9 platelets 198 wbc 6.5 LDH incr total bilirubin 3.4 (high indirect one) normal AST and ALT. -When RBC are incubated in hypotonic saline -> Hb is released. Dx? and what is the pt most at risk of developing?
Dx is HEREDITARY SPHEROCYTOSIS this causes HEMOLYTIC ANEMIA - most at risk of PIGMENTED GALLSTONES So: - the +ve osmotic fragility test described (lysing of rbc when incubated in hypotonic saline) = aka Hereditary spherocytsosis - the anemia + incr LDH + indirect bilirubinemia => HEMOLYTIC ANEMIA signs (espec incr LDH) - hemolytic anemia -> can lead to pigmented gallstones due to incr bilirubin from lysed RBC which precipitates as calcium bilirubinates and form stones in GB. NB - sexual hx was a distractor - could think of cirrhosis of liver due to HepB/C = but AST and ALT would have been HIGH (here normal)
Q82. 32yo - african-american male - dx of acute prostatitis - is given trimethoprim-sulfamethoxazole (bactrim) - then develop dark urine and anemia - high reticulocytes count most likely DX?
G6P DH deficiency - which can arise when exposed to drugs like anti-malarials, trimethoprim-sulfamethoxazole (bactrim) and fava beans - it is X-linked = ie only males. - G6P-DH is essential to keep adequate conc of NADPH which reduces ROS. - if DEF -> rbc more vulnerable to ROS and hemolyse which is induced by infections, drugs, fava beans (an oxidant) p/c - anemia with pallor - indirect bilirubinemia (jaundice) - hemoglobinemia - hemoglobinuria (dark-urine) - high reticulocytes (precursors of rbc) cos to compensate rbc destruction. this is not MAHA cos rbc would be destroyed in small bv and are associated with DIC, thrombocytopenic purpura and HUS.
Q91 5yo boy -slow bleeding after dental extraction - hx of hemarthrosis after minor trauma -give DESMOPRESSIN which stops the bleeding. -most likely Dx? - what is the most likely target for Desmopressin?
HAEMOPHILIA A -target is ENDOTHELIUM cos desmopressin (DDAVP) acts as analogue of vasopressin which releases F8 from endothelium. F8 is synthesized in liver but stores in endothelial cells. -Haem A cos its factor 8 def -> p/c are prolonged bleeding after surgeries and easy bruising and haemarhtrosis (can lead to joint deformity). But do not see petechiae (cos characteristic of platelet disorder). - NB desmopressin has no effect on HaemB (f9 def) and it is used for mild-moderate HaemA. - Desmopressin (ADH analog) is also used for tx DI cos it incr reabs of water. - NB desmopressin has no effect on synthesis of F8 in liver but just release of it from endothelium.
Recurrent hemarthroses is suggestive of what disease?
HEMOPHILIA (f8 or 9 def) -> hemarthroses Ie bleeding in joint space.
Q174. 34yo man - 2 wks of easy bruising and fatigue - also recent URT infection - no lymphadenopathy or hepatosplenomegaly - lab shows: Hb 7.0 rbc count 1.8 [4.7-6.1] MCV 90 reticulocytes 0.1% (low) [0.5-1.5%] platelets 88 leukocytes 2.5 blood smears: - normocytic and normochromic rbc of peripheral bloods. - what would we see in the bone marrow biopsy?
HYPOCELLULAR marrow filled with FAT CELLS and FIBROTIC STROMA - Dx is Aplastic Anemia - this is due to pancytopenia + very low reticulocytes count + LACK of splenomegaly. - bone marrow examination is needed to distinguish (both have pancytopenia w/o splenomegaly): a. MYELOPROLIFERATIVE DISEASE where there is increased bone marrow cellularity with megaloblastic anemia and in older ppl b. APLASTIC ANEMIA where thery HYPOcellularity and these are replaced by fibrous stroma and fat cells. Thus in aplastic anemia there is DRY TAP when do aspiration of BM
lysing of rbc when incubated in hypotonic saline - is a test for which disease?
Hereditary spherocytosis = +Ve osmotic fragility test -leads to hemolytic anemia.
what lab test is used as marker for HAEMOLYSIS?
LACTATE DEHYDROGENASE (INCR) - LDH is often used as a marker of tissue breakdown as LDH is abundant in red blood cells and can function as a marker for hemolysis. -it can also be used as a marker of myocardial infarction.
Q8. A 23-year-old -recent immigrant from Africa presents to his physician with a - rapidly enlarging jaw mass. -The mass is biopsied, and numerous - mitotic figures and apoptotic bodies are observed on histologic exam. = "starry sky" - Which genetic feature is most likely present in this tissue? - what is the most likely diagnosis?
Overexpression of C-MYC oncogene, t(8;14) BURKITT LYMPHOMA (african type). - classical jaw involvement - almost all are with EBV infections (not in sporadic ones). - histology shows = starry sky appereance cos of macrophages and apoptotic bodies with medium-sized lymphocytes. - 90% have translocation of chr 8 onto 14. (t8,14). which causes overexpression of CMYC oncogene - burkitt lymphoma responds well to high dose chemo and excellent prognosis. - nuclei with coarse chromatin - several nucleoli - many in mitosis. the other 2 types of burkitt lymphoma happens SPORADICALLy (where there is often a ileo-cecal valve mass but do not have EBV infections) and in HIV patients.
in which leukemia do we see with rod-shaped cytoplasmic inclusions called Auer rods with many azurophilic granules?
PROMYELOCYTIC LEUKEMIA (FAB M3 type) - this is a type of AML characterised by - acquired HYPERcoagulability and bleeding (DIC)
what is the difference between the p/c of PROTEIN C DEF with WARFARIN vs VIT K DEF?
PROTEIN C DEF with WARFARIN tx - imbalance of pro/anti-coag - more pro-coagulation cos both would decr anti-coagul - more thrombosis of microbv eg skin necrosis VIT K DEF - less F2,7,9,10 - so more likely BLEEDING tendency not hypercoagul.
Q47. 50yo - started on WARFARIN for new onset AF - 36hrs later develops painful lesion (big bruise with skin necrosis) on arm what is the most likely cause?
PROTEIN C DEFICIENCY - warfarin started as prophylaxis against thromboembolism from AF - WARFARIN-induced NECROSIS happens when there is PROTEIN C/S DEF - protein C is a natural anticoagulant - this with warfarin (another anticoag) -> leads to transient imbalance of pro/anti-coagulation with relative Exagerrated Hypercoagulability with thrombotic occlusion of microvasculature and skin necrosis. tx is discontinuing warfarin and give FRESH-FROZEN PLASMA to replenish protein C def. NB!!! - if it was VIT K DEF -> less F2,7,9,10 -> lead to BLEEDING TENDENCIES NOT HYPERCOAGUL state. cos less coagulation factors.
Q84 -45yo male - periodic epigastric abd pain and fatigue - mild hepatomegaly - CT shows pancreatic calcifications - RUQ US shows no gallstones - low hb - high MCV - low platelets what process is reduced which is responsible for anemia? most likely dx?
REDUCED THYMIDINE (PYRYMIDINE) BASE SYNTHESIS CHRONIC PANCREATITIS (due to abn pain, hepatomeg, pancreatic calcific) due to ALCOHOL abuse (most common cause) - the MEGALOBLASTIC ANEMIA in alcoholics is typically due to to FOLATE DEF - folate is needed for synthesis of purine and pyrimidine bases. - so def of folate in megaloblastic anemia leds to decr synthesis of nucleic acids like thymidine. XS alcohol -> macrocytosis and thrombocytopenia too (like here)
Q125. 12yo African boy -p/c - fever, chest pain and SOB. - hx pf 2 hospitalisation due to abn pain -> resolved by analgesia and hydration. - today the hematocrit count is 23% and reticulocyte count is 9%. - kid dies and autopsy shows spleen is firm and brown. - most likely reason?
SICKLE CELL ANEMIA -> SPLENIC INFARCTION. - when someone p/c multiple with abd pain relieved by analgesia and hydration and African = think of SCA cos pain is due to vaso-occlusion. - this time pt presented with CP and sob ie acute chest syndrome due to pulm vaso-occlusive crisis precipitated by infections. - especially in hom SCA-SS -> see multiple splenic infarction which with time cause spleen to shrunk (ie not palpable) and brown colour (cos of hemosiderosis from extravascular hemolysis) and fibrotic = this is called autosplenectomy ie it eventually regresses to a smaller size within the body.
sickle cell rbc can lead to obstruction of BV - name 3 main symptoms of where?
SICKLE CELL RBC lead to occlusion of bv and cause: 1.auto infarction of the spleen (in all SCA) 2.episodic venous thrombosis 3. avascular necrosis of the femur (very susceptible in SCA)
Q139. neonate born at 32wks - mother is 23yo primagravida - Apgar score is 8 and 9 at 1min and 5min. - before delivery mum had corticosteroids to incr fetal lung maturation and analgesia for pain - which vit deficiency in premature baby can be life-threatening in 1st week of life?
VITAMIN K - fat soluble vit (ADEK) - needed for F2,7,9,10 - 2 forms - Ki from green vegetables and menaquinone from gut bacterial flora. - common vit K def in preterm newborns due to: - hepatic immaturity - low vit K in breast milk - sterile GI tract - poor placental transfer of vitK. -Vit K def -> risk of hemorrhage disease of newborn where see skin, GI and intracranial bleeding. Tx: - parenteral vitK to all infants NB - breast milk has def of vit K and D - vit D def occurs at 6months of age if no supplements given and only breast fed.
Q63. 20yo -african-american male - p/c haematuria - Hb electrophoresis shows - 60% HbA - 40% HbS what is most likely to be true and what is the dx?
dx - pt is HETEROZYG HbAS ie has TRAIT (this is when there is 35-40% of HbS) they are PROTECTED FROM - sickle cell crises - aplastic crises - sequestration cirses - these protection are due to presence of >50% of normal HbA - most HbAS hetez are asymptomatic and may get haematuria. - the answer is that they will be RELATIVE PROTECTION from PLASMODIUM FALCIPARUM (malaria) cos if incr sickling of rbc with the parasite they would be removed by spleen macrophages. - they will have -normal MCHC - normal reticulocytes count NB - when add SODIUM METABISULFATE to these HbAS (trait) -> rbc will sickle = SICKLING TEST IS +VE
in follicular lymphoma what chr translocation happens and what is overexpressed?
follicular lymphoma (type of non-hodgkin) - - (14:18) translocation - overexpression of the antiapoptotic BCL-2
Q113 - see image 35yo male - notices non-tender cervical lymphadenopathy on shaving - lymph node histology is shown. (shows follicles) - what would the cytogenetic analysis show?
image shows FOLLICULAR LYMPHOMA (a type of NHL). = a lymphoproliferative disorder. - follicular lymphoma is made up of B-cell tumour with centrocytes and fewer centroblasts. -> obscure the normal architecture of LN. - 80-90% of these lymphomas have T(14,18) translocation -> OVEREXPRESSION OF BCL2 (Anti-apoptotic gene) -> tumour. NB -Burkitt lymphoma has translocation of C-MYC gene = t(8,14) and histology shows lymphocytes and starry sky appearance cos of high prolif and high rate of apoptosis. - overexpression of N-MYC -> in neuroblastoma and small cell lung ca. - while t(9,22) BCR-ABL Philadelphia chr is seen in CML - a myeloprolif disorder (not lymphoprol like here).
Give 3 major causes of splenic infarction?
o Sickle cell anemia o Infectious endocarditis o Myeloproliferative disorders.
what is the differential Dx of pancytopenia WITHOUT splenomegaly?
severe vitamin B12 def folic acid deficiency aplastic anemia, leukemia, myelodysplastic syndrome Bone marrow examination can distinguish a myeloproliferative disease with increased bone marrow cellularity from aplastic anemia (hypocellular with fat cells and fibrous stroma)
what is the SCHILLING TEST used for? how does it work?
to help differentiate between different causes of vitb12 def eg - dietary - ab against IF (pernicious anemia) - malabsorption like coeliac disease how? if give ORAL LABELLED vitb12 and then UNlabeled IM injection of vitb12 -> - normal urine excretion of labeled vitb12 = dietary cause - low urine excretion of labeled vitb12 = impaired intestinal abs due to pernicious anemia (lack of IF) or malabsorption To Differentiate malabsorption vs pernicious anemia give radiolableed vitb12 + Intrinsic factors -if normal urine excretion = dx for pernicious anemia - if low urine excretion of b12 -> malabsorption syndrome ( pancreatic insuffic, bacterial overgrowth (eg diphyllobothrium latum), short gut syndrome, coeliac disease)
Q6. A 11-year-old Caucasian female newly diagnosed with - iron-deficiency anemia mentions that - her menstrual bleeding lasts 7-8 days. - She also notes occasional gingival bleeding. - Her platelet count is normal. - Further evaluation reveals that her platelets aggregate normally in response to ADP but - poorly with addition of ristocetin. This abnormality is caused by a deficiency of?
vWF DEFICIENCY (von Willebrand disease) - vWF is synthesised by endothelial cells and stored in endothelium and platelets - binds to GP rec on platelets - has 2 functions: 1. platelet aggregation +adhesion to endothelial collagen 2. carrier of F8. (imp for activation of F10 and then thrombin) - abn platelet aggregation in response to RISTOCETIN but normal to ADP. - If deficient : 1. decr platelet adhesion and aggregation: - mucocut bleeding like gingival - easy bruising - prolonged bleeding after trauma - prolonged periods (menses) - have normal platelet count - incr bleeding time - RISTOCETIN AGGREGATION TEST is used to measure vWF-dep platelet aggregation -> it activates the GP rec for vWF on platelets so more vWF can bind to it. BUT if there is low vWF like here then poor platelet aggregation in presence of ristocetin. 2. vWF normally acts as a carrier for F8 and prolongs its half-life(from 2hrs to 12hrs). - so less vWF means less available F8 so more bleeding (cos less thrombin produced and less fibrin) -have prolonged partial thromboplastin time (APTT) = intrinsic pathway - tx: - desmopressin (adh) to stimulate vWF release from endothelium.
