Bikalpa Khatiwada MDCM CCFP (EM)

Rosen’s

EMRAP

Pocket Medicine

UptoDate

Canadian Blood Services

Pepid

Oncological

Transfusion

Hemolytic

Coagulopathy

Platelet Disorders

Reversing Anti-platelet / Anti-coagulants

50 year old male

PMHx: HTN, MI – stents, Colon Ca – chemo last week. Unsure about mets.

1. Fever at home >38.5deg.

2. Altered level of conscious without fever

3. Acute shortness of breath

4. Back pain

Physical: Temp 39, HR 100, BP 110/70, Sat 95% RA, Glucose 10mmol/L

Labs: • Na 135, K 3.5, Urea 5.5, Creat 90.• WBC: 2.0, ANC 0.3, hgh 100, plts 150.

Diagnosis: ?

Clinical Features Fever. 7-14days post chemo.

Diagnosis Absolute neutrophil count < 0.5 x 109/L or <1.0 x 109/L and

expected to drop to less than 0.5.

Diagnositic Strategies CBC, electrolytes, pt, ptt, U/A and culture (even without pyuria), blood culture x2 (take one from central line) and gram stain CXR

What to avoid: rectal temps and DRE, NG tubes increase sinusitis risk.

What is not needed: sputum, nares, throat or stool cultures

Causes: 85% bacterial (60-70% gram positives) Bacterial: pseudomonas aeruginosa (less with abx

given during therapy) Staph. aureus, staph. epidermidis,

Fungal: Candida Albicans Virals: HSV, VZV, CMV

Antibiotics are given during therapy: Septra, Quinolones

Management is based on low and high risk.

Who is low risk:• No obvious source• No SIRS criteria

• ANC > 0.1 x109/L

• Good follow up and reliable patient.

Low Risk Patient: • Cipro 750mg q12h, clavulin 500mg q8h • Pen Allergy: Replace clavulin with clindamycin

High Risk Patient• Pip-tazo 3.375g IV q6h• Ceftazidime 1g IV q8H (cefepime – same

dosing)

• Pen Allergy: Cipro 400mg IV q12 + tobramycin 5mg/kg IV q24 + vancomycin 1g IV q12h

• Add vanco to above if worried about line sepsis, mrsa risk.

PE: T 37.5deg, BP 110/70, sat 95%, RR 16, glucose 10.

Diagnosis:

1. Tumour Lysis Syndrome2. Hypercalcemia3. Brain mets with herniation

• Clinical Features• Typically post Chemo patient (1-5days).• High risk: if renal disease, dehydrated, large tumour size, advanced disease.

• Confusion, tetany from hypocalemia• ARF: Insufficiency from uric acid nephropathy• Dysarrythmia from hyperkalemia

• Diagnosis• Hyperkalemia, Hyperphosphatemia,

Hyperuricemia, Hypocalcemia .

Admit.

Hydrate following urine output (100ml/h)

Hyperuricemia (use allopurinol 300-600mg/d prophylactic, 600-900mg if active TLS)

Avoid alkalinization if hyperkalemic or hypocalcemic (more calcium phosphate crystals in urine)

Dialysis • Indications: K > 6mmol/l, Creat>880mmol/l, volume

overload, symptomatic hypocalcemia, uric acid>580mmol/l, phospate>3.2mmol/l

Clinical Features• “Moans, groans and psychic overtones”• General: itching• Neuro/psychiatric: mood changes• Renal: polyuria,polydipsia, • Gastro: abdopain constipation, • Cardiovascular: htn, dysrhythmia, digitalis sensitivity.

• Causes: Bone mets, lymphomas (NHL), or from PTH hormone like agents produced by tumours.

Diagnosis• Calcium high and Albumin

Admit

Oral and IV hydration (NS 5-6L/day) +/- furosemide• If urine out put adequate, add furosemide (40-80mg U IV) to

inhance calcium output

if Ca>3.5mmol/L (check albumin)• Bisphosphonates: Pamidronate 90 mg iv infusion over 4-

24hours (takes 4 days) • Calcitonin 4-8 IU/kg IM/SC

Watch for hypokalemia (q4hours)

Clinical features• Increased ICP• Bleed or Mass• Uncal : Temporal lobe compresses brainstem:

one eye dilated, ipsilateral paralysis.• Central: upper pons pushed caudal

altered LOC, small reactive pupils, cheyne – stokes breathing. No focal signs• Tonsillar: cerebellar tonsills into foramen magnum:

Altered LOC, Headache, vomiting, meningismus.

Diagnosis: CT head

Transfer

IV mannitol (1gm/Kg IV q6-8h) Hyperventilation (paCO2 30) IV steroids (dexamethasone 10-100mg IV loading dose)

ClinicalCauses: Malignant effusion, radiation pericarditis

Signsjvp up, muffled heart sounds, and hypotension (beck’s triad)facial and neck swelling

DiagnosisEKG: Electical alternansPhysical: Pulsus paradoxisEDE ULTRASOUND Before CT PE protocol.

ManagementPericardiocentesis (if done emergently: 4% mortality, 17% complication rate). Ultrasound guided might be usefulRecollection can occur so a catheter is usefulImprove RV volume. (fluids and avoid diuretics,nitrates)

Clinical• BackPain• Weakness• Urinary retention / loss of rectal tone. • Sensory loss

Diagnosis• xray (70-90%)• MRI if any abnormality

• if unclear: CT spine first step• watch out for epidural hematoma (differential Diagnosis)

Management/Disposition• Dexamethasone 10mg IV loading (start even before testing)

then 4mg IV q6h• Contact oncologist

Clinical Features Similar to Tumour Lysis Syndrome Can get renal uric stones, obstruction, renal failure.

Diagnosis: Uric Acid levels (>530umol/l)

Management If Uric Acid >530umol/L

Allopurinol (300-600mg/day)

Fluids (urine output 2L/day)

Alkalinise urine (NaHCO3, acetozolamide, +/- mannitol to mantain urine flow)

+/- Dialysis

Oncological

Transfusion

Hemolytic

Coagulopathy

Platelet Disorders

Reversing Anti-platelet / Anti-coagulants

Symptom/Sign Based:• Fever

• Dyspnea

• Hypotension

• Uticaria

Even before ABCs:

• STOP THE TRANSFUSION!• Notify transfusion services.

65 year old female. Lower GI Bleed but stable. Receiving 2U pRBCs. GI consultant to come and see.

Handover patient as she is getting her second unit of blood.

Nurse comes to you and says....

1. “Doc, that patient getting the 2 units of blood, now has a fever of 38.5deg.”

2. “Doc, she is really has having a hard time breathing”

3. “Doc, she is really confused and her BP is 80/40.”

Clinical• If temperature increases more than 1 deg

during transfusion and is >38 C within 4 hours of transfusion

Diagnosis

• Febrile non-hemolytic Transfusion reaction (FNHTR)

• Acute Hemolytic Transfusion Reaction• Bacterial infection/contamination

Management• Stop Transfusion• Acetominophen • Benedryl if FNHTR• If Signs of SIRS

Blood cultures and gram stain from patient and from blood product

Check for blood type incompatibility Check urine for hemoglobinuria (seen with ABO

incompatibility) Broad spectrum antibiotics (G+ve and –ve)

Disposition:• Admit: bacterial sepsis or acute hemolytic rxn.

Clinical:• SOB during transfusion or shortly there after

Diagnosis• Transfusion Related Acute Lung Injury (TRALI)

In 6hours of transfusion.• Transfusion associated Circulatory Overload

(TACO) CHF from poor cardiac history and rapid rate of

transfusion.• Anaphylaxis

Management• Stop the Transfusion• ABCs, IV access, O2 and monitor and stat CXR• TRALI

Supportive – mech. Ventilation when needed. 72% needed supp. Vent. 10% mortality. Lasts up to

72h. Steriods and Diuretic use controversial

• CHF (TACO) Diuretics Reduce transfusion rate (up to 4h) if clinically able.

• Anaphylaxis

Disposition• TRALI: ICU• CHF: depends on clinical status.• Anaphylaxis: 4 hour observation.

(Urticaria: if less than 2/3 of body can restart once benedryl is on board)

Clinical• >30mg Hg drop in systolic or diastolic

pressure.

Diagnosis/Differential• Acute Hemolytic transfusion rxn.• Bacterial sepsis• Severe febrile non hemolytic transfusion rxn• Bradykinin mediated hypotension• TRALI

Management: Stop the transfusion IV, O2, Monitor Manage according to differential.

Bradykinin related hypotension:• Mostly with platelet transfusions• Especially on patients with an ACEi• Care supportive and don’t restart

transfusion.

Working in small ER. MVC from local highway comes in. Your patient has a mid-shaft femur

fracture and BP is labile.• You start transfusing pRBC and hoping to

transfer patient but weather is bad and Ornge is delayed.

• After the nurse hangs the fifth pRBC, you wonder what might be the issues with massive transfusion?

Definition:• Greater than 10 Units of pRBC in 24hours.

Dilutional Coagulopathy• Avoid waiting for INR to climb (>1.5) and plts to drop (<50 x 109/L)• Ratio is not fixed but 1:1:1 suggested. pRBC: FFP: Plts.• Pediatrics: if >20m/kg prbc/h, FFP 15ml/kg, plts 5ml/kg, cryoppt 2ml/h (for the

fibrinogen)

Hypothermia

• If giving more than 5 units of pRBC consider warmer.

Electrolyte Abnormalities• Citrate in blood products can bind Calcium and Magnesium:

Parasthesia, arrythmias, hypotension, Manage with 1 gram (1 amp of 10%) of Calcium Chloride over 10min.

• Hyperkalemia If old blood products used.

Oncological

Transfusion

Hemolytic

Coagulopathy

Platelet Disorders

Reversing Anti-platelet / Anti-coagulants

36 year old male immigrant from Ghana Complaining of fever, abdominal and

back pain No travel but two days ago treated for

urethritis in clinic with Cipro.

OE: T 38.5, BP 110/80, HR 100, Sat 99% Jaundiced.

Urine: Hematuria.

Clinical• Jaundice, Pallor• Fever, back and abdominal pain, altered LOC.

Diagnosis• CBC• Reticulocyte count (>2% expected if bone marrow active)• Blood smear (schistocytes = intravascular, spherocytes =

extravascular)• Haptoglobin (low if intravascular hemolysis)• LDH elevated (from rbc turnover)• Bilirubin (indirect) elevated (if hemolytic)• Direct and indirect Coombs test (if immune mediated)

Clinical• Signs of hemolysis• Membrane of RBC not able to handle oxidative stress due to G6PD

deficiency• African and Mediterranean Decent

Diagnosis Labs for Hemolysis positive Smear: Heinz Body or Bite Cells

Management• Supportive and Transfusion as needed

Drugs to Avoid• Antibiotics: Cipro, Nitrofurantoin, Sulfa• Anti malarials• Methylene blue

25 year old male with history of Sickle Cell Disease. Presents to ER with acute chest pain.

Trait vs Disease• Single vs. Both beta gene mutation

Clinical• Vaso - Occlusive crisis

Acute Chest syndrome Priapism Hand and foot syndrome in pediatrics

• Hematological Crisis Aplastic syndrome Acute sequestration / splenic infarct

• Infectious Crisis Watch for encapsulate Bacteria: S. Pneumonia, H. Influenza

Diagnosis• CBC and Reticulocyte count to look out for aplastic crisis (if less than 2% and

drop in hemoglobin)• Smear: sickle cells , howell jolly bodies.• Type and screen.• Electrolytes• LFTs • UA• Imaging: CXR, Abdominal US, Bone Xrays according to history.

Management• Hydration (D5 1/2ns at 150-200cc/h) – watch for CHF (especially in acute chest

syndrome): Need probably 2-4L of fluid.• Oxygen 2-4L/m Nasal prongs• Aggressive Anagesia: try to have protocol for these patients.

• Transfuse if aplastic anemia or splenic sequestration. Watch out for iron overload and antigen exposure.

• Exchange transfusion if neurological symptoms or CVA in children.• Hydroxyurea (15-35mg/kg/day PO): long term management

Oncological

Transfusion

Hemolytic

Coagulopathy

Platelet Disorders

Reversing Anti-platelet / Anti-coagulants

CoagulopathyPlatelet Disorders

35 year M Presents to ER with Epistaxis History of Hemophilia A/B/von

Willebrand’s Disease.

Difficulty with Controlling epistaxis using usual techniques.

Any other options?

Clinical: • Hematoma, Hemarthrosis, bruising, bleeding.• Hemophilia A (x linked factor VIII defect)• Hemophilia B (factor IX defect)

Diagnosis:• CBC: potential anemia from bleeding• INR normal, PTT elevated (normalises with mixing study)

Management:• Hemophilia A/von Willebrand Disease:

Cryoprecipitate (2-4bag/10kg ) has factor VIII, FFP ddAVP: 0.3mcg/kg IV in 50ml NS over 30min q 8h.

• Hemophilia B: Factor IX (1st choice) and FFP (15-20ml/kg)

Oncological

Transfusion

Hemolytic

Coagulopathy

Platelet Disorders

Reversing Anti-platelet / Anti-coagulants

30 year old Male Rash on his legs

1: Confusion but hemodynamically stable

2: Confused and hemodynamically unstable

3: Recent viral illness, otherwise well

Definition: less than 150 x 10 9 /L

Causes:• Reduced Platelet Production: chemo, alcoholism, thiazide diuretics,

leukemia, MDS.

• Splenic sequestration

• Destruction: Heparin Induced Lupus Clopidogrel

Diagnosis

CBC and differential (just plts or more)

Peripheral smear (schistocytes)

If anemia: reticulocyte count, ldh, haptoglobin, bilirubin

If hemolytic: INR, PTT, fibrinogen, d-dimer, coombs, ANA.

Clinical:• pentad: purpura, hemolytic anemia, delerium, renal failure (hematuria,

proteinurea) and fever: 40%• ADAMS 13 protease activity reduced.• Causes: idiopathic, drugs (clopidogrel, quinine),

Diagnosis:• CBC: Low platelets, Anemia• Blood smear: schistocytes. • Coombs: negative• INR, PTT, Fibrinogen normal.• Liver enzymes: indirect Bili elevated.

Management:• Admit (+/- ICU)• Steriods: Prednisone 1mg/Kg PO or methylprednisolone 1gm/kg/d IV.• Plasma exchange with FFP (aka plasmaphersis) mortality drop 90->17%

FFP replaces ADAMTS-13• Splenectomy• AVOID Platelet TRANSFUSION (makes clotting worse)

Clinical:• Bloody diarrhea• E.coli O157:H7, shigella• Shiga toxin binds to endothelial cells

Diagnosis• CBC: Low platelets, Anemia, • Blood smear: schistocytes • INR, PTT, Fibrinogen normal

• Thrombocytopenia, Microangiopathic hemolytic anemia, Renal failure (more so than TTP), Neurologic symptoms less than TTP.

Management:• Similar to TTP

Clinical• Bleeding diathesis• Coagulopathy• Microangiopathic hemolytic Anemia• Look for the primary cause (sepsis, trauma, amniotic fluid emboli,

transfusion)• Sick patient.

Diagnosis• CBC: Anemia, low platelets.• Smear: Schistocytes.• Coagulation studies: low fibrinogen, INR and PPT elevated, D-Dimer and

fibrinogen degradation products elevated.

Management• Manage the Primary issue (sepsis, trauma)• If Hemorrhagic: Replace blood products: pRBC, Platelets, FFP, cryoppt (I, V,

VIII), Factor VIIa (last resort)• If Fibrin Deposition: IV Heparin (5-10u/kg/h) if clotting dominates the

clinical picture.

Clinical• A diagnosis of exclusion• Post viral infections in young children• Chronic form seen in adults (F>M)

Diagnosis• Isolated low platelets and no other obvious etiology

Management• Steroids (1mg/kg/day PO Prednisone)• IVIG (1g/kg/d IV x 2-3days)• Avoid platelet replacement unless active bleeding.• Disposition: Based on hemodynamic stability and follow up

with hematology.

Test ITP TTP/HUS DIC HSP

Platelets Low Low Low Normal

Hgb Normal Low Low Normal

smear normal schistocyte schistocyte Normal

INR/PTT normal normal elevated normal

Oncological

Transfusion

Hemolytic

Coagulopathy

Platelet Disorders

Reversing Anti-platelet / Anti-coagulants

70 year old male Epistaxis Not able to stop the bleeding.

He is on:• Antiplatelet agent (ASA/Clopidogrel)• Anticoagulant (Warfarin, LMWH,

Dabigatran)

ASA (t1/2 = up to 30hours) Clopidogrel (t1/2 = 10 hours)* Ticagrelor (t1/2 = 7-9 hours)

Reversal:• Platelets. • DDAVP:

0.3ug/kg/dose in 50ml NS over 30min IV

Heparin:

• Protamine: 1mg per 100u Heparin used Slow Push at 5mg/min. Watch out for side effects.

Especially with fish allergy.

• Low molecular weight Heparin: 1mg per mg enoxaprin, per 100u dalteparin. if >8hours use half the dose (0.5mg/mg)

Non Urgent:• American Association of Hematology

Decreasing / Holding Reversing Testing

Acute Bleed• Vitamin K: 10mg IV • Prothrombin Concentrate Complex

(Octaplex): 40ml IV x 1• Fresh Frozen Plasma: 10ml/kg IV

150mg BID

Reversal:

• 60ml Octaplex IV• 2mg of Factor VIIa IV• ? Hemodialysis

Oncological

Transfusion

Hemolytic

Coagulopathy

Platelet Disorders

Reversing Anti-platelet / Anti-coagulants