Case #1: Unexpected Pre-op Labs 62 yo man scheduled for bilateral - - PDF document

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Case Discussions in Hematology:

Musings from the UCSF Hematology (e)Consult Service

Management of the Hospitalized Patient

Andrew D. Leavi4, MD

October 21, 2016

Case #1: Unexpected Pre-op Labs

62 yo man scheduled for bilateral Total Hip Arthroplasty has the following pre-op CBC that shows an unexpected anemia. CBC: WBC: 7.1 Hgb 7.8 Hct 29.2 Plt 288 Consult to Heme: 1. Why is he anemic? 2. Please eval asap, patient in pain and needs surgery. Surgery cancelled until you give us an answer. 3. He is a physician

How do you proceed? What do you want to know?

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Case #1: Unexpected Pre-op Labs

MCV, Retic, Smear, and…

Case #1: Unexpected Pre-op Labs

No Retic on record

Major Spine Surgery

Ferritin 9 (low); Iron sat 3% (low)

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Case #1: Progression to Iron Def. Anemia

Modified from Harrison’s 18th ed

POINTS:

• 1. Microcytosis is late to the table. Trends can be useful.
• 2. Low ferritin should not be ignored when SI and %sat are normal

*

*SI = serum iron

Case 2: Anemia – Need a Marrow Biopsy?

64 yo woman: “Persistent microcytic anemia. Does she need a bone marrow biopsy?” Most recent CBC that prompted the referral: There was no retic & no smear to review when asked to see patient

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Case 2: Anemia – Need a Marrow Biopsy?

The Mighty EMR

• 1. Stable MCV
• 2. Iron studies in early 2015 not c/w iron deficiency
• 3. Hemoglobinopathy eval in early 2015…

Case 2: Anemia – Need a Marrow Biopsy?

NORMAL <1.0 2.2 - 3.2 96.7 – 97.8

Normal? Abnormal? Tells you what?

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Erythropoiesis: Hemoglobin Switching

(Hgb: 2 alpha & 2 “beta-like” [aka, non-alpha; 3 options]) Embryo Fetus Birth Adult 6 mo.

Globin chain synthesis (%)

50

α α β δ γ ζ

ε

HgF α2γ2 (75) HgA α2β2 (25) HgA α2β2 (96-98) HgA2 α2δ2 (2-3) HgF α2γ2 (<1)

Hoffman et al. Hematology 2000

Alpha: Chromosome 16 Beta-like: Chromosome 11

Erythropoiesis: Hemoglobin Switching

(Hgb: 2 alpha & 2 “beta-like” [aka, non-alpha; 3 options]) Embryo Fetus Birth Adult 6 mo.

Globin chain synthesis (%)

50

α α β δ γ ζ

ε

HgF α2γ2 (75) HgA α2β2 (25) HgA α2β2 (96-98) HgA2 α2δ2 (2-3) HgF α2γ2 (<1)

Hoffman et al. Hematology 2000

Alpha: Chromosome 16 Beta-like: Chromosome 11

So… No Bone Marrow Biopsy YES Alpha Gene Analysis

4 Alpha Genes: αα αα/αα αα αα αα/α- ( (Silent c.) αα αα/-- ( (Trait) α-/α- ( (Trait) α-/-- ( (Hg H)

• -/-- (

(hydrops)

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Anemia?....then always MCV, Retic, Smear, and… EMR trends

CASE #3: Anemia: What would you do?

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Case #3: Does She Need RBC Transfusion?

34 YO woman with hx of Fe-deficiency anemia admitted for RLQ pain. Was found to be anemic and to have a R gonadal vein thrombosis The primary team wants to anti-coagulate for the gonadal vein thrombosis but is concerned because she (i) is so anemic and (2) is having her menses.

Heme Consult 200mg Venofer: IV Iron Sucrose 100mg 200mg 100mg

WBC HGB HCT PLT RETIC

What is Your IV Iron Experience

• A. Never/almost never use it
• B. Typically use Ferric Carboxymaltose (Injectafer)
• C. Typically use Iron Dextran (InFed)
• D. Typically use Ferumoxytol (Feraheme)
• E. Typically use Iron Sucrose (Venofer)
• F. Typically use Ferric Gluconate (Ferrlecit)
• G. Typically use other

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Parenteral Iron: Options

Name Company Dose IV Infusion Iron Dextran Watson 1-2 grams 4 hours (InFeD) acetaminophen and diphenhydramine (prior reputation for anaphylaxis) Ferumoxytol AMAG 510 mg 10-15 min (Feraheme) Pharmaceutical (30mg/ml) acetaminophen or often nothing Iron Sucrose Vifor 200 mg 1-1.5 hours (Venofer) acetaminophen and diphenhydramine Ferric gluconate Sanofi-aventis 125 mg 1-1.5 hours (Ferrlecit) acetaminophen and diphenhydramine Ferric Carboxymaltose Vifor 750 mg 30-60 Min (Injectafer) acetaminophen and diphenhydramine

Hepcidin & Iron RegulaIon

Body’s iron store Synthesis Duodenum Macrophages Reduced Serum Iron Hepcidin

Fe2+

BMP6 IL6 Ferroportin Hepcidin Ferroportin Hepcidin

• +

Fe2+ Fe2+

MACROPHAGE DUDOENAL VILLOUS CELL

10/25/16 9 ANSWER: NO But, tell me more about your iron deficiency….

Case #3: Does She Need RBC Transfusion?

For years. Very heavy and prolonged menstrual periods. Struggled with oral iron on and off for years. Factor 8 55 (43-168) vWF Antigen 40 (42-191) Ristocetin Co-Factor 33 (42-191)

Case #4: Prolonged aPTT

22 yo man evaluated for possible living-related kidney transplant.

Chemistries – fine Infectious Disease Testing – fine CBC – all normal values PT/INR – 12.4/1.0 aPTT 34. On repeat 35 (normal: 22.4 – 32.7) Can we take this patient safely to surgery?

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Case #4: Prolonged aPTT

22 yo man evaluated for possible living-related kidney transplant.

• Most common cause of an isolated prolonged aPTT?

Concern for bleed? Concern for clot? Neither? Factor VIII 120 (nl) Factor IX 145 (nl) Factor XI 112 (nl) Factor XII 41 (low)

Factor XII deficiency has no known clinical consequence

Case #5: Prolonged PT

28 yo woman G2P1 36 weeks pregnant admitted for hypertension and proteinuria, concern for pre-eclampsia. INR 3.1. You are called as they are concerned about her coagulopathy. PT 30.2 WBC 11.2 (ANC 8.8; ALC 1.8) INR 3.1 Hgb 11.5 aPTT 22.1 MCV 79 Fibrinogen 525 Plt 262

• She was feeling well prior to this admission
• Eats a balanced diet and was not on any medications other than her

prenatal vitamins.

• Afebrile

What is on your differential diagnosis for her prolonged PT?

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XII XIIa XI XIa IX IXa VIIIa X Xa Va II IIa (thrombin)

Fibrinogen Fibrin

VIIa VII

X-linked Fibrin XIIIa

Ca++/PL Ca++/PL

Kallikrein HMWK

INTRINSIC

EXTRINSIC

COMMON

TF/VIIa TF

Isolated Prolonged PT

(EXTRINSIC)

• Early Liver Dz
• Early Vit K
• Warfarin
• Early DIC
• F VII def/inhib

PT

Case #5: Prolonged PT Tests Ordered:

Mixing Study: Factor VII activity: <6% (54-169%)

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Case #6: Bleeding in the Neuro ICU

Ø 73 y.o. man w/PMH of cardiac stent ten years ago w/o MI in usual state of health. Ø Watching TV with his wife, got up & went to adjacent room. The wife heard a "loud crash" in the other room and found husband down on the ground w/ some shaking movements that quickly resolved. Ø Brought to ER: Man had no recollection of the event and denied any pain or

• complaints. EMS note enlarged right pupil and repetitive speech but o/w

neuro intact. No other medical complaints or trauma. Ø Taking aspirin. Not on any other anticoagulants. Ø IN ER: Neuro exam non focal but he was confused. Ø Non contrast head CT obtained.

Case #6: Bleeding in the Neuro ICU

R R

Non Contrast Head CT:

• 1. Large right holohemispheric extra-axial collection with an apparent epidural component spanning the right parietal lobe

measuring 2.4cm. There is right-to-left midline shift measuring 1.7 mm and mass effect on the falx.

• 2. Adjacent bi-hemispheric areas of punctate hyperdensity at the vertex and superior parietal lobe which could represent

hemorrhagic contusions or shear injury in the correct clinical setting.

• 3. Comminuted and displaced frontoparietal calvarial fractures extending to the sagittal suture with depression/step off measuring

2mm superiorly and inferiorly

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Case #6: Bleeding in the Neuro ICU

Timeline of Events:

6:44pm CT results communicated to ER To OR for emergent right craniotomy for hematoma evacuation 9:59 Brief Op Note: R craniotomy and hematoma evacuation Condition at end of operation: Stable IN OR: 2 units platelets; 2 P-RBC 10:15 Shortly after arrival to ICU – Hypotensive to 50s. Neo qtt and NS bolus Developed “Coagulopathy - INR 2.1 post-op for unclear reasons, may be 2/2 EBL of 800. Pre-op LFT's normal, but will recheck. Transfusing 2 FFP.”

OR 2RBC 2 FFP Call to Heme

Hemoglobin 12.0 9.3 9.4 Platelets 202 105 136

What is the problem?

• Severe liver dz
• Warfarin - supra-Tx
• Severe Vitamin K def.
• High dose heparin (Xa & IIa)
• Dilutional
• DIC
• A/hypo/Dysfibrinogenemia
• Paraproteins (Factor X)
• Common Pathway def./inhib.
• Lupus anticoagulant (rarely; F II*)

Causes of Prolonged PT and aPTT

• Early Liver Dz
• Early Vit K
• Warfarin
• Early DIC
• F VII def/inhib

Prolonged PT Prolonged PT & aPPT

*Factor II = Prothrombin BLEED NO BLEED

• F VIII*
• vWD
• F IX*
• Heparin
• F XI
• F XII
• Contact factors
• Lupus anticoag (clotting)

Prolonged aPPT

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Case #6: Bleeding in the Neuro ICU

Timeline of Events:

6:44pm CT results communicated to ER To OR for emergent right craniotomy for hematoma evacuation 1 U platelets given; T&C 4U PRBC, 2U FFP stat 9:59 Brief Op Note: R craniotomy and hematoma evacuation Condition at end of operation: Stable IN OR: 2 units platelets; 2 P-RBC 10:15 Shortly after arrival to ICU – Hypotensive to 50s. Neo qtt and NS bolus Developed “Coagulopathy - INR 2.1 post-op for unclear reasons, may be 2/2 to EBL of 800. Pre-op LFT's normal, but will recheck. Transfusing 2 FFP.”

OR 2RBC 2 FFP Call to Heme

Hemoglobin 12.0 9.3 9.4 Platelets 202 105 136

Sudden onset of PT and PTT prolongation DDX: Dilution or DIC Asked them to add fibrinogen & d-dimer & Repeat PT, PTT, fibrinogen & d-dimer

Case #6: Bleeding in the Neuro ICU

Timeline of Events:

10U Cryoppt & 2U FFP

Platelets 202 105 136 49 114 112 101

2+2 FFP 2 Plt OR 2RBC

1. Re-accumulation of Right EDH/SDH which has enlarged and is causing worsening mass effect, including right to left midline shift, concern for subfalcine herniation. 2.

• 2. Interval blooming of bilateral intraparenchymal hemorrhages with surrounding edema,

consistent with axonal injury, of the parietal and frontal lobes near the vertex. 2:35am CT Brain w/o Contrast:

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Prolonged PT and aPTT DON’T FORGET TO CHECK FIBRINOGEN IF ACUTE…. Think Dilutional and Consumption

Disseminated Intravascular Coagulation

DIC

Uncontrolled thrombin Generation (too much Tissue Factor) Consume platelets and coagulation factors Fibrin deposits in the microcirculation Secondary fibrinolysis Diffuse bleeding D-Dimers RBC destruction and hemolysis Ischemic tissue damage Vessel patency Multiple Organ failure Thrombosis

Adopted from Harrison’s Principles of Internal Medicine

1 2 * * * *

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Case #7: Young Man Feeling Punk

23 yo man experienced 4 days of progressive fatigue, mild headache, and occasional palpitations. He then had difficulty focusing at work and co-workers said he looked pale. Went to local urgent care. CLINIC EXAM: T 37.1 HR 117 BP 144/68 RR16 100%RA Pale, no acute distress, no scleral icterus Hear, lung and abdominal exams all normal Labs drawn at clinic: CBC: WBC 13.4, Hg 5.1, Hct 15.9, Platelets 264 Chem: 137/3.6/102/28; Bun 13, Creatinine 0.74 PMH: No prior surgeries or significant medical problems. No GI or GU complaints. The patient was sent to the UCSF ED for evaluation. AT UCSF ER: Patient is as described. BP 144/68, HR 117, Temp 98.8 (37.1), Res 16 O2 Sat 100% (room air) WBC 13.8, Hgb 5, Hct 15.9, MCV 113, Plt 271

Case #7: Young Man Feeling Punk

MORE LABS BACK: Reticulocyte count 487K/uL LDH 413, AST 26, ALT 14, Alk Phos 55, T.bili 2.1, D.bili 0.2 Additional labs pending…

10/25/16 17 What is your leading diagnosis at this time?

• A. B12 or Folate deficiency
• B. MDS
• C. Hypothyroidism
• D. Iron deficiency
• E. Thalassemia with aplastic crisis

F. Hemolytic anemia

• G. Sickle cell disease
• H. Liver disease

I. Other

Case #7: Young Man Feeling Punk

MORE LABS BACK: WBC 13.8, Hgb 5, Hct 15.9, MCV 113, Plt 271 Reticulocyte count 487K/uL LDH 413, AST 26, ALT 14, Alk Phos 55, T.bili 2.1, D.bili 0.2 Additional labs pending…

Case #7: Young Man Feeling Punk

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You send Type and Crossmatch to the Blood Bank. You ask them to set up 4 units of blood and you want two units asap. 30 minutes later blood bank says that his antibody screen is positive, there could be a delay. AND… 30 minutes later they say that he has an antibody and they are working to identify it so that they can provide compatible units. They ask: What do you want to do? You want to ask: Auto or Allo Ab? How many more tubes do you need for a phenotype?

Case #7: Young Man Feeling Punk

Order an RBC PHENOTYPE on the patient

PRIOR to him getting any blood products!

DATE WBC HGB HCT MCV PLT RETIC

Case #7: Young Man Feeling Punk

P-RBC 2 1

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Case #7: Young Man Feeling Punk

Lets discuss the EMR Blood Bank info Direct Coombs = DAT

Warm-reacting Ab Warm-reacting Ab, Anti-M, Cold-reacting Ab

Case #7: Young Man Feeling Punk

Lets discuss the EMR Blood Bank info

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Case 8: A guy with bruising

56 yo man c/o one month of spontaneous ecchymoses on arms and legs, but a large one on his leg brought him to the ER Denies prior problem with bleeding. Circumcision – no problem Multiple wisdom teeth removed in his 20’s– no problem Was in the army – no problem Denies family hx of bleeding disorders Labs: CBC: WNL, including Hgb 14.1, Platelets 285 PT 12.6 (INR 1.0), aPTT 37.2 (nl 22-32) Lytes, BUN, Creat, LFTs - normal

Thoughts?

XII XIIa XI XIa IX IXa VIIIa X Xa Va II IIa (thrombin)

Fibrinogen Fibrin

VIIa VII

X-linked Fibrin XIIIa

Ca++/PL Ca++/PL

Kallikrein HMWK INTRINSIC

EXTRINSIC COMMON

TF/VIIa TF

Isolated Prolonged aPTT

(INTRINSIC)

• F VIII*
• vWD
• F IX*
• Heparin
• F XI
• F XII
• Contact factors
• Lupus anticoagulant (clotting)**

aPPT

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Case 8: A guy with bruising

ACQUIRED HEMOPHILIA Ø Bleeds soft tissue and CNS, not the typical joint bleeds of inherited hemophilia Ø Extent of aPTT prolongation is not predictive of bleeding risk Ø Auto-immune problem Ø Is apparent in a mixing study and a Factor 8 assay

Thank you all who attended this session. I had more cases available, but this is where we ended. I think it makes more sense to only post content we covered, otherwise the “interpretation” can be a tad sketchy. Hope to see you again in a future year, and I encourage you to send me your ideas for hematology/transfusion medicine cases you would like to see addressed in the

• future. Your feedback helps keep the course relevant

and fresh. Best, Andy Leavitt (andrew.leavitt@ucsf.edu)

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