Hematology (5-10%) Complete

Question 1

Non-cancer-associated Proximal DVT and PE: ( ______ first line, if no contraindications)

– Provoked
• Tx for _______ months (up to ___ months)

– Unprovoked or chronic risk factor
• Tx for _____ months then ______

Answer 1

Non-cancer-associated Proximal DVT and PE: (DOAC first line, if no contraindications)

– Provoked
• Tx for 3 months (up to 6 months)

– Unprovoked or chronic risk factor
• Tx for 3 - 6 months then assess bleeding risk; continue indefinitely with regular reassessment of risk: benefit

Question 2

Cancer-associated Proximal DVT and PE: ( _______ if no contraindications)
Low/mod bleeding risk: ________ therapy (1B) while active cancer (which means metastasis and also during +6 months in remission)

_______ preferred where bleeding risk is high

Answer 2

Cancer-associated Proximal DVT and PE: (LMWH or DOAC if no contraindications)
Low/mod bleeding risk: indefinite therapy (1B) while active cancer (which means metastasis and also during +6 months in remission)

LMWH is preferred where bleeding risk is high:
- high-risk GI lesions (e.g. angiodysplasia, varices)
- unresected intraluminal GI/GU cancer
- high-risk intracranial lesion (glioma, RCC, melanoma)
- Child-Pugh class B/C
- platelet < 50
- recent bleed
- DOAC Drug Interactions

Question 3

DOAC:
CONTRAINDICATION IN:
1. _________________
2. _________________
3. _________________
4. _________________
5. _________________

Answer 3

CONTRAINDICATION IN:
1. Liver failure: Child-Pugh B and C
2. Anti-phospholipid antibody syndrome: arterial thrombosis, triple positive, small vessel thrombosis (livedo reticularis, nephropathy)
3. Pregnancy AND Breastfeeding
4. Drug-drug interactions (e.g. doxorubicin, cyclosporine, carbamazepine, phenytoin, azoles, protease inhibitors – bleeding risk): apix/riva CYP3A4/P-gp; dabi/edox P-gp)
5. Platelets < 50

Question 4

PAXLOVID (ritonavir) and DOAC?

Answer 4

PAXLOVID (ritonavir) = contraindicated to use w apix and riva

Question 5

When to Use Warfarin?
MNEMONIC?

Answer 5

Be CALM

Breastfeeding
– Therapeutic anticoagulation while breastfeeding [INR generally 2- 3 depending on the indication for anticoagulation]. DOACs contraindicated, LMWH is OK.

CKD (stage 4/5)
– INR generally 2-3 depending on the indication for anticoagulation

Antiphospholipid Ab Syndrome
– APLA Syndrome associated VTE [INR 2-3] (triple positive)

LV Thrombus (+ “Likes warfarin” – pt on warfarin stable for years)
– LV Thrombus (NB observational and 1 small RCT suggests DOAC may be non inferior to VKA)

Mechanical Valve
– Mechanical valves [INR 2.5-3.5 – mitral, INR 2-3 - aortic]

Question 6

Role of thrombolysis in VTE:
DVT: ________________

Answer 6

• limb-threatening DVT (phlegmasia cerulea dolens)

Question 7

Role of thrombolysis in VTE:
PE: ________________

What about intermediate-risk PE” (i.e.: RV dysfunction on ECHO/CT, elevated troponin)

Answer 7

hemodynamic instability (sBP <90 for over 15 mins) with no high bleeding risk (Gr 2B)

What about intermediate-risk PE” (i.e.: RV dysfunction on ECHO/CT, elevated troponin): Not indicated

Question 8

Cancer-Associated VTE – Outpatient Prophylaxis?

Answer 8

Question 9

When to consider full-dose anticoagulation in Distal (calf) DVT?

Answer 9

• Severe symptoms
• Multiple deep veins involved
• Active cancer
• ≥5 cm long
• Close to the popliteal vein
• Irreversible risk factor
• +Ddimer
• Progression on repeat U/S

Question 10

Superficial femoral vein is ___________

Answer 10

Superficial femoral vein is DEEP VEIN (MISNOMER)

Question 11

Superficial Vein thrombosis and anticoagulation:

• ≤3 cm from saphenofemoral junction = ___________________
• > 3cm from SFJ and ≥5 cm long = ___________________
• > 3cm from SFJ + <5cm long = ___________________

Answer 11

• ≤3 cm from saphenofemoral junction =
  full dose anticoagulation x 3 months
• > 3cm from SFJ and ≥5 cm long =
  prophylactic anticoagulation x 45d (fondaparinux 2.5 mg sc daily or rivaroxaban 10 mg po daily)
• > 3cm from SFJ + <5cm long =
  NSAIDs and monitor with serial U/S. ** Exceptions: prophylactic anticoagulation in pregnancy, cancer, surgery, trauma, prior hx of SVT/DVT

Question 12

Subsegmental PE and Anticoagulation:
Next step?

Answer 12

Leg dopplers
If positive: Def anticoagulation

If negative: Consider treatment if: active cancer/other
thrombotic risk, symptomatic, high D-dimer

Question 13

Reversal Agents for Anticoagulants:

Warfarin:

Non-bleeding:
• INR >9: __________________________
• INR 4.5-9: __________________________

Non-life-threatening bleed:
• __________________________

Life-threatening bleed/imminent procedure:
• __________________________

When to use FFP?

Answer 13

Non-bleeding:
• INR >9: hold warfarin + VitK 2.5-5 mg po
• INR 4.5-9: hold warfarin + decrease dose

Non-life-threatening bleed:
• Vit K + supportive

Life-threatening bleed/imminent procedure:
• IV Vit K + prothrombin complex (PCC)
– PCC dosing per INR:
INR 1.5-3: PCC 1000U; INR 3-5: PCC 2000U; INR> 5: PCC 3000U

When to use FFP? PCC is superior to FFP for warfarin reversal. CHOOSING WISELY CANADA – do not use FFP for VKA reversal if PCC is available

Question 14

Reversal Agents for Anticoagulants:

LMWH/Heparin: __________________________

Answer 14

Protamine 25-50 mg

Question 15

Reversal Agents for Anticoagulants:

DOACs:

Non-life-threatening: __________________________

Life-threatening bleed: __________________________ +

1. Dabigatran:
   • __________________________
2. Apixaban/Rivaroxaban/Edoxaban:
   • __________________________
   • __________________________

Answer 15

Non-life-threatening: supportive

Life-threatening bleed: supportive +

1. Dabigatran:
   • Idarucizumab (Praxbind) 2.5g x 2 doses; consider dialysis (~65% removal in 4 h)
2. Apixaban/Rivaroxaban/Edoxaban:
   • 4-factor PCC (e.g. Octaplex, Beriplex); 2000U (can be repeated)
   • Andexanet alfa (not available in Canada)

Question 16

Primary hemostasis

Clinical Presentation:
• _________________________________
• _________________________________
• _________________________________
• _________________________________

Labs:
Platelets?
Coagulation profile?

DDx
1. _________________________________
_________________________________

2. _________________________________
   ↓Quantity == e.g. _________________________________
   ↓ Quality == e.g. _________________________________

Answer 16

Primary hemostasis

Clinical Presentation:
• Mucocutaneous bleeding
• Easy bruising
• Heavy menstrual bleeding
• Petichiae (low plts)

Labs: +/- ↓ plts, often coags normal

DDx
1. VWF Deficiency
Von Willibrand Disease (VWD)

2. Plt Disorder
   ↓Quantity == e.g. ITP
   ↓ Quality == e.g. ASA, uremia, congenital

Question 17

Secondary Hemostasis:

Clinical Presentation:
• ___________________________
• ___________________________
• ___________________________

Labs:
___________________________

DDx [see slides specific to INR/PTT]
1. ___________________________
• ___________________________
• ___________________________
• ___________________________

2. ___________________________
   • ___________________________
   • Medications: ___________________________

Answer 17

Secondary Hemostasis:

Clinical Presentation:
• Hemarthrosis
• Intramuscular bleeding
• Retroperitoneal bleeding

Labs: abnormal coag. tests

DDx [see slides specific to INR/PTT]
1. Coagulation factor deficiency
• Hemophilia A (Factor VIII)
• Hemophilia B (Factor IX)
• Warfarin (II, VII, IX, X)

2. Coagulation factor inhibitor
   • Idiopathic/various diseases
   • Medications: DOACs

Question 18

Approach to Isolated Elevated PT or aPTT

Answer 18

Question 19

Approach to elevated aPTT & PT

Answer 19

Question 20

VWF :↑ levels in _________________
VWF :↓ levels in _________________

Answer 20

VWF:↑ levels in stress, estrogens, pregnancy
VWF: ↓ levels in blood group O

Question 21

Von Willebrand Disease Diagnosis

• Type 1:
• Type 2:
• Type 3:

Answer 21

Von Willebrand Disease Diagnosis

1. Type 1:
   - Quantitative deficiency (↓VWF:Ag [<30%] = ↓VWF Rco [<30%] ie. concordant; ratio>0.7)
   – VWF < 30% or VWF 30-50% + abnormal bleeding = diagnostic

2 Type 2:
- Qualitative deficiency of VWD (↓/↔VWF Ag [<30-200%], ↓↓VWF:Rco [<30%] ie. discordant; ratio<0.7)

3. Type 3:
   - No VWF produced (↓VWF:Ag [<5%] =↓VWF:Rco [<5%]; ↓↓ factor VIII)
   - Behaves like Hemophilia A

Question 22

Von Willebrand Disease

Treatment:
1. Acute Bleeding/Peri-Op?

2. Heavy menstrual bleeding?

Answer 22

Von Willebrand Disease:

Treatment:
1. Acute Bleeding/Peri-Op:
– DDAVP: boosts vWF level (can work for Type 1; not in type 2B/2N or 3)
– Blood products: plasma-derived concentrates of vWF and FVIII (e.g. Humate P)

2 Heavy menstrual bleeding:
- TXA +/- OCP

Question 23

Immune Thrombocytopenia (ITP)
Treatment

1) NOT BLEEDING/MILD MUCOCUTANEOUS BLEEDING & PLT >30:
_________________________________________________________

2) NOT BLEEDING & PLT < 30
• 1st line:______________________________________________
• 2nd line:______________________________________________

3) ACTIVE BLEEDING
• ______________________________________________
• Life-threatening: ______________________________________

Answer 23

Immune Thrombocytopenia (ITP)
Treatment

1) NOT BLEEDING/MILD MUCOCUTANEOUS BLEEDING &
PLT >30 • Watch and wait

2) NOT BLEEDING & PLT < 30
• 1st line: Pred 0.5-2mg/kg or Dex 40 mg X 4d, IVIG (if C/I to pred; caution: hemolysis), anti-D (RhD+; caution: hemolysis)
– FLIGHT: MMF + steroids

• 2nd line: splenectomy, rituximab, TPO-R agonists

3) ACTIVE BLEEDING
• Steroids + Tranexamic Acid +/- IVIG

• Life-threatening: Plt transfusion +/- splenectomy

Question 24

Immune Thrombocytopenia (ITP)
Treatment
PREGNANCY?
- Indication for treatment?
- How to treat?
- Platelet cut off for delivery?
- Platelet cut off for neuraxial anesthesia?

Answer 24

Immune Thrombocytopenia (ITP)
Treatment
PREGNANCY:
• Tx if bleed, plt <30, delivery or plt<50+≥36 wk GA

• Steroids or IVIG (Pred>Dex as Dex crosses placenta)

• plt>50 for delivery,
- plt>80 for neuraxial anesthesia

Question 25

Secondary ITP treatment If significant bleeding and HCV/HIV: HCV? _________________ HIV? _________________

Answer 25

Secondary ITP treatment 1. If significant bleeding and HCV/HIV: HCV: use IVIG (NO ROLE FOR STEROIDS) HIV: Steroids or IVIG

Question 26

DO NOT MISS: Evan’s Syndrome?

Answer 26

DO NOT MISS: Evan’s Syndrome = ITP + hemolytic anemia - - 2⁰ Autoimm/Connective tissue diseases - - Difficult to treat, frequent relapse

Question 27

Heparin-induced Thrombocytopenia 4T score?

Answer 27

Question 28

Management of HIT: 1. Anticoagulant Choice: - IV? ____________________________ - SC? ____________________________ - PO? ____________________________ - Pregnancy? ____________________________ 2. Duration of treatment? - No thrombosis = ____________________________ - Thrombosis = ____________________________

Answer 28

Management of HIT: Anticoagulant Choice: - IV: Argatroban, Danaparoid - SC: Fondaparinux - PO: Warfarin, DOACs - Warfarin: start when **PLT ≥ 150** + overlap with non-heparin anticoagulation ≥5d once INR 2 – 3 - DOACs: (rivaroxaban 15 BID x 3 wks if VTE or until plt recovery, if no VTE --> Rivaroxaban 20 mg daily) - Pregnancy: Danaparoid preferred Duration: - No thrombosis = min. until platelet recovery (>150), max 3 mon - Thrombosis = 3-6 mn

Question 29

Thrombotic Microangiopathy (TMA)? Peripheral blood film? Platelets? Thrombi?

Answer 29

Thrombotic Microangiopathy (TMA): – Micro-angiopathic hemolytic anemia (MAHA) -> schistocytes – ↓Plt – Microvascular thrombi --> end organ damage

Question 30

TTP – a Hematologic Emergency: Treatment?

Answer 30

–PLEX within 4-8h • FFP to bridge: 3-4u then 1u q2h –No plt transfusion unless life-threatening bleed –Steroids (Pred 1 mg/kg/d or Solumedrol IV 1g/day) –Folic acid 5 mg daily –+/- ASA if ↑ trop/CNS symptoms –DVT proph when plt >50 –Caplacizumab or Rituximab can be considered in refractory cases

Question 31

Hemolytic Anemia: Spherocytes

Answer 31

Spherocytes: • Warm autoimmune hemolytic anemia (IgG) • Hereditary spherocytosis • Delayed hemolytic transfusion reaction

Question 32

Hemolytic Anemia: Agglutination

Answer 32

Agglutination: • Cold autoimmune hemolytic anemia (IgM) • Paroxysmal cold hemoglobinuria

Question 33

Warm Autoimmune Hemolytic Anemia: Diagnosis? Etiology? Treatment? 1st Line: ____________ 2nd Line: ____________

Answer 33

Diagnosis: - Hemolysis labs - Blood film: spherocytes - DAT: +IgG (+/- C3d) Etiology: 1o vs 2o – 2o: Lymphoproliferative disease (e.g. CLL), autoimmune (e.g. SLE), drugs (e.g. methyldopa, NSAIDs) Treatment: 1st line: - Prednisone 1 – 1.5 mg/kg/day 2nd line: - Splenectomy (>8-12 mon) - Rituximab

Question 34

Cold Autoimmune Hemolytic Anemia: Diagnosis? Etiology? Treatment? 1st Line: ____________ 2nd Line: ____________

Answer 34

Diagnosis: – Hemolysis labs – Blood film: agglutination – DAT +ve C3d (= IgM antibody) – Thermal amplitude: significant if ≥28⁰C Etiology: 1o vs 2o – 2o: Infection (mycoplasma pneumonia, EBV), lymphoproliferative disorder (MGUS, Waldenstroms, lymphoma) Treatment: – #1: Warm patient! – Treat underlying cause – **Steroids not helpful** – Rituximab for refractory cases

Question 35

PCC (Prothrombin complex concentrate) vs Plasma in HIT?

Answer 35

PCC has heparin = do not use in warfarin reversal w HIT, give ffp instead

Question 36

Platelet Refractoriness?

Answer 36

Question 37

Myeloid Disorders 1. Acute Myeloid Leukemia (AML) – too many __________ myeloid cells (i.e. myeloid blasts) 2. Myeloproliferative Neoplasms (MPNs) – too many ________ myeloid cells • too many RBCs = ________________ • too many platelets = ________________ • too many granulocytes = ________________ 3. Chronic Myelomonocytic Leukemia (CMML) – features of ________________ and ________________ • too many ________________ • myeloid cells are ________________ 4. Myelodysplastic Syndrome (MDS) – bone marrow ________________ • ________________ hematopoiesis • myeloid cells are ________________

Answer 37

Myeloid Disorders 1. Acute Myeloid Leukemia (AML) – too many immature myeloid cells (i.e. myeloid blasts) 2. Myeloproliferative Neoplasms (MPNs) – too many mature myeloid cells • too many RBCs = Polycythemia vera (PV) • too many platelets = Essential thrombocytosis (ET) • too many granulocytes = Chronic Myelogenous Leukemia (CML) 3. Chronic Myelomonocytic Leukemia (CMML) – features of BOTH MPN and MDS • too many monocytes • myeloid cells are dysplastic 4. Myelodysplastic Syndrome (MDS) – not enough myeloid cells (cytopenias) -> bone marrow failure • ineffective hematopoiesis • myeloid cells are dysplastic

Question 38

Lymphoid Disorders 1. Acute lymphocytic leukemia (ALL) – too many __________ lymphoid cells 2. Lymphoproliferative disorders (LPDs) – too many __________ lymphoid cells • __________: burden of disease is in the peripheral blood • __________: burden of disease is in lymph node • Waldenstrom Macroglobulinemia /Lymphoplasmacytic lymphoma 3. Plasma cell dyscrasias – Too many __________ cells → overproduction of a __________ • MGUS → smoldering myeloma → multiple myeloma • Primary amyloidosis

Answer 38

Lymphoid Disorders 1. Acute lymphocytic leukemia (ALL) – too many immature lymphoid cells (i.e. lymphoid blasts) 2. Lymphoproliferative disorders (LPDs) – too many mature lymphoid cells • CLL: burden of disease is in the peripheral blood • Lymphoma: burden of disease is in lymph node • Waldenstrom Macroglobulinemia /Lymphoplasmacytic lymphoma 3. Plasma cell dyscrasias – Too many plasma cells → overproduction of a single antibody / light chain • MGUS → smoldering myeloma → multiple myeloma • Primary amyloidosis

Question 39

Acute Leukemia: Diagnosis?

Answer 39

≥ 20% blasts in peripheral blood or bone marrow*

Question 40

Blast cells + Auer rods + DIC THINK: ___________

Answer 40

APL (Acute Promyelocytic Leukemia)

Question 41

APL • T(__;__) • ________ mortality from ____: Urgent treatment? ______

Answer 41

• T(15;17) PML-RARA • ↑early mortality from DIC: - Intracranial hemorrhage - Blood clots Urgent treatment: ATRA (all-trans-retinoic acid)

Question 42

Acute Leukemia Associated Emergencies: 1. Tumor lysis __ K, __ PO4, __ uric acid (UA), __ Ca Treatment: 1. ______________ 2. ______________ 3. ______________ 4. ______________

Answer 42

↑ K, ↑ PO4, ↑ uric acid (UA), ↓ Ca Treatment: 1. Manage hyper-K, correct ext. lytes 2. IVF (target UO 80-100 mL/m2/h) AND EITHER: 3. Allopurinol OR 4. Rasburicase if: AKI, ↑↑ uric acid (>535 umol/L), no response to allopurinol (NOT in G6PD def)

Question 43

Acute Leukemia Associated Emergencies: 2. Leukostasis Treatment: 1. ______________ 2. ______________ MOST IMPORTANT 3. ______________ 4. ______________

Answer 43

Treatment: 1. IVF 2. Cytoreduction (e.g hydroxyurea, leukapheresis, induction chemo) 3. TLS prophylaxis 4. Avoid transfusion

Question 44

Polycythemia vera: Risk stratification (for thrombosis) LOW RISK: Age _____ and ________ HIGH RISK: Age ____ or _______ history Treatment: EVERYONE: __________, optimize __________, __________ HIGH RISK: __________ (__________ if young or pregnant)

Answer 44

Risk stratification (for thrombosis) LOW RISK: Age < 60 and no thrombosis history HIGH RISK: Age ≥ 60 yo or thrombosis history Treatment: EVERYONE: ASA 81 mg, optimize CV risk factors, Hct < 45% with phlebotomy (CYTO-PV NEJM 2013) HIGH RISK: cytoreduction with Hydroxyurea (interferon if young or pregnant)

Question 45

Essential Thrombocythemia (ET) Treatment: Very low risk (no thrombosis, age<60, JAK2-): __________________ Low risk (no thrombosis, age<60, JAK2+): __________________ Intermediate risk (no thrombosis, age≥60, JAK2-): __________________ HIGH RISK (age≥60 and JAK2+ or thrombosis hx): __________________ JAK2+ with CV risk factors: __________________ *Hold __________________ if plt > 1000-1500 or acquired vWD

Answer 45

Essential Thrombocythemia (ET) Treatment: Very low risk (no thrombosis, age<60, JAK2-): observation Low risk (no thrombosis, age<60, JAK2+): ASA 81 mg Intermediate risk (no thrombosis, age≥60, JAK2-): ASA 81 mg HIGH RISK (age≥60 and JAK2+ or thrombosis hx): add hydroxyurea (interferon if young or pregnant) JAK2+ with CV risk factors: ASA 81 mg BID *Hold ASA if plt > 1000-1500 or acquired vWD

Question 46

Leukoerythroblastosis? Definition? ___________________ Differentials? The presence of leuko-erythroblastosis raises concern for transformation from ___/__ to ____________________

Answer 46

Leukoerythroblastosis? Definition: (left shift in myeloid series with **myelocytes/ metamyelocytes/ blasts** along with **nucleated RBCs**) Differentials? - GCSF - infection/marrow stress - myelophisitic processes (ie. metastatic cancer to bone) - MPNs including myelofibrosis/CMML The presence of leukoerythroblastosis raises concern for transformation from PV/ET to prefibrotic myelofibrosis.

Question 47

CLL: Presentation: • Peripheral blood: "_________” cells Diagnosis: • ______________________ *Do not need _______ to make dx

Answer 47

CLL: Presentation: • Peripheral blood: “smudge” cells Diagnosis: • peripheral blood flow cytometry *Do not need BMBx to make dx

Question 48

CLL Treatment options: Which is associated with bleeding and Atrial fibrillation?

Answer 48

CLL Treatment options: Tyrosine kinase inhibitors i.e. Ibrutinib (SE = bleeding, A.fib)

Question 49

Lymphoma Classification + Treatment

Answer 49

Question 50

Chimeric Antigen Receptor (CAR)-Therapy Toxicities: 1. Cytokines release syndrome (CRS) Sx? Labs? Tx? 2. Immune effector cell-associated neurotoxicity (ICANS) Sx? Tx?

Answer 50

Chimeric Antigen Receptor (CAR)-Therapy Toxicities 1. Cytokines release syndrome (CRS) Sx? Fever, tachypnea, headache, tachycardia, HTN, rash, hypoxia due to cytokines storm Labs: elevated CRP/ferritin Tx based on CRS grade: supportive care, +/-**steroids, +/- tocilizumab** 2. Immune effector cell-associated neurotoxicity (ICANS) due to disruption in BBB, cytokines Sx: aphasia, tremor, altered LOC, impaired cognition, motor weakness, seizures, cerebral edema Tx: supportive care, CNS imaging, seizure prophylaxis/treatment; Tx concurrent CRS

Question 51

Plasma Cell Dyscrasias

Answer 51

Question 52

Waldenstrom’s Macroglobulinemia: DEFINITION: AKA ______________ AND ______________ in the peripheral blood Other key features to distinguish from others?

Answer 52

AKA Lymphoplasmacytic lymphoma (an indolent lymphoma with features between B-cells & plasma cells) AND Monoclonal IgM in the peripheral blood Other key features to distinguish? Hepatosplenomegaly, lymphadenopathy

Question 53

Bone Marrow Failure Syndromes?

Answer 53

Myelodysplastic Syndrome (MDS) – Cytopenia(s) + dysplastic cells/genetic abnormalities/blasts Aplastic anemia (AA) – Hypocellular bone marrow – Primary vs. secondary Paroxysmal nocturnal hemoglobinuria (PNH) – Bone marrow failure – Hemolysis – Thrombosis

Question 54

Myelodysplastic Syndrome (MDS): Definition:

Answer 54

Question 55

Myelodysplastic Syndrome (MDS): Presentation: • _______ pt. w/ a _____ (often ___ Hb + ____ MCV) • Blood film: ________________ neutrophils, ____________ platelets, macrocytosis, _____ retics Diagnosis? _______________

Answer 55

Presentation: • Older pt. w/ a cytopenia (often ↓Hb + ↑MCV) • Blood film: hypolobated/hypogranular neutrophils, hypogranular platelets, macrocytosis, ↓ retics Diagnosis: • Bone marrow biopsy/aspirate: – Hypercellular (usually) +/- ring sideroblasts – Dysplasia >10% – Blasts <20%

Question 56

Paroxysmal Nocturnal Hemoglobinuria (PNH) Characterized by? 1. _______________ 2. _______________ 3. _______________ 4. ________________ Work-up? Diagnosis? • ___________________ • Can overlap with ___________________ Treatment?

Answer 56

Characterized by? 1. Bone marrow failure 2. Chronic intravascular (+ extravascular) hemolysis --> uncontrolled complement activation 3. Thrombosis (venous + arterial) --> common site = splanchnic, hepatic 4. thrombosis in atypical locations (ie. abdominal or cerebral veins), anemia Sx, hemolysis Sx (jaundice, red urine), pHTN Sx, decr NO Sx (erectile dysfxn, dysphagia) Work-up? • Hemoglobinuria (rare), hemolysis labs, Cr (renal failure from pigment nephropathy) Diagnosis? • Peripheral blood flow cytometry (loss of CD55 + CD59) • Overlap w/ aplastic anemia Treatment? • Anti-coagulate if thrombotic events – No role for primary prophylactic anticoagulation • Eculizumab or pegcetacoplan (complement inhibitors) - ↓ hemolysis + transfusion need (not curative)

Question 57

Answer 57

Blast with Auer rod If you see blasts with Auer rods, think APL Arrow = Auer rod

Question 58

Answer 58

Teardrops Think myelofibrosis (B symptoms, high LDH, splenomegaly, cytopenias, leukoerythroblastosis)

Question 59

Answer 59

CLL

Question 60

Answer 60

ROULEAUX Associated with multiple myeloma as well as inflammation, pregnancy (high ESR states)

Question 61

Answer 61

Spherocyte Spherocytes lack central pallor and are smaller than normal RBC. Think immune-mediate hemolysis (e.g. auto or allo immune)

Question 62

Answer 62

Hyper-segmented Neutrophil ≥6 lobes = hypersegmented. Think megaloblastic anemia (e.g. folate or B12 deficiency)

Question 63

Answer 63

Schistocytes (aka fragments) All arrows pointing to examples of schistocytes. Think TMA (eg. TTP)

Question 64

Answer 64

Malaria

Question 65

Answer 65

Sickle Cell

Question 66

Blood Product “Modification" Indications for CMV-negative blood:

Answer 66

- Intrauterine transfusion

Question 67

Blood Product “Modification" Indications for irradiated blood - prevent transfusion-associated ______: 1. _____________ 2. _____________ 3. _____________ 4. _____________

Answer 67

Indications for irradiated blood - prevent transfusion-associated GVHD: Ø T cell deficiency Ø Hodgkin’s lymphoma Ø Chemotherapy with purine antagonists or purine-like antagonists Ø HSC transplant recipients: • Allogeneic: for life • Autologous: for 3 months

Question 68

Blood Product “Modification" Indications for washed platelets: 1. ______________ 2. ______________ 3, ______________

Answer 68

Indications for washed platelets: Ø Anaphylaxis to transfusion NYD Ø Recurrent/severe allergic transfusion reactions Ø IgA deficiency with no IgA deficient donor available

Question 69

Thrombocytopenia: 1) Rule out ___________________ 2) Should I be worried? – Other lineages down? → __________________ – Abnormal coags? → _______________________ – Recent heparin → _________________________ – Recent transfusion → _____________________ – Is this sepsis?

Answer 69

Thrombocytopenia: 1) Rule out pseudo-thrombocytopenia • Secondary to EDTA-associated agglutinins • Repeat in citrated tube 2) Should I be worried? – Other lineages down? → Marrow process, MAHA, Evans – Abnormal coags? → DIC, APLA – Recent heparin → HIT – Recent transfusion → Post-transfusion purpura – Is this sepsis?

Question 70

Pancytopenia ddx Primary? Secondary?

Answer 70

Pancytopenia ddx Primary 1. Paroxysmal Nocturnal Hemoglobinuria (PNH) 2. Aplastic Anemia 3. Leukemia 4. MDS 5. Myelofibrosis Secondary 1. Deficiency - B12/Folate, anorexia, êT4 2. Infection – granulomatous, HIV, sepsis 3. Iatrogenic – chemo, rads, ETOH 4. Infiltrative – mets, amyloid, Gaucher 5. Hypersplenism

Question 71

B12 deficiency or syphilis?

Answer 71

Distinguish Neuro B12 deficiency from Neuro Syphilis – BOTH: Mental status changes/Dementia – Pupils: B12: Normal - Pupils: Syphilis: Argyle Robertson (small, no reaction to light but does accommodate) – B12 = subacute combined degeneration of cord = corticospinal tract (UMN weakness, increased tone in legs, hyperreflexia/clonus) AND dorsal column (dec. vibration, proprioception) – Syphilis = “Tabes Dorsalis” = dorsal column (vibration, proprioception impaired) and dorsal roots (absent reflexes in LE). Unlike B12 deficiency, tone/power should be normal.

Question 72

Differentials: DIC vs other hemolysis

Answer 72