Haema/Onco

Anticoagulants

Blood Transfusion Reactions

Hyperleukocytosis and Leukostasis

Oncologic Emergencies

Thrombocytopenia: ITP/TTP/HUS/HIT/DIC

Tumor Lysis Syndrome

Anticoagulants

Warfarin - 10, 9, 7, 2

Heparin - fXa and thrombin (FII)

LMWH - fXa

Fundaparinux

Direct Thrombin Inhibitors:

Thrombocytopenia: ITP/TTP/HUS/HIT/DIC

Thrombocytopenia (Dr Arora, USC Essentials)

ITP

• childhood: acute, self-limiting, 2-3 weeks post immunization or infection
• adult: insiduous, chronic, no preceding illness
• symptoms: platelet-type) bleeding (superficial, mucosal, gingival, petechiae) vs deep bleed/coagulopathy (intraarticular)
• pathophys: impaired platelet production and destruction (T cell, B cell, spleen)
• Tx: steroids, IVIG, platelets (only when sick, will be destroyed anyway), splenectomy
• RhoGAM: induces mild hemolysis in Rh+ patients, spares igG coated platelets from splenic destruction
• New drugs: thrombopoietin receptor agonists, stimulates platelet production

TTP

• FATRN: Fever, MAHA, Thrombocytopenia, renal, neuro
• anemia, thrombocytopenia +/- neuro
• think TTP if anemia, thrombocytopenia, hematuria (intravascular hemolysis)
• uremia is rare
• wax and wane: platelet clot is unstable (becomes stable only when with fibrin)
• common: obese, black, female, HIV, drugs (quinine, plavix, ticlopidine)
• untreated: >90% mortality; treated: 10-20% mortality
• platelet worsens
• Pathophys: ADAMTS-13 (protease) is lacking which supposed to cleave vWF
• ULvWF, released from endothelium when stressed (trauma/infection), attaches to platelets = vWF monomers
• in TTP, platelet microthrombi (with no fibrin) = microangiopathic hemolytic anemia (increased uncon bilirubin, increased LDH, normal fibrin/fibrinogen)
• New tests: ADAMTS-13 level, activity, inhibitor, vWF gel electrophoresis, DNA analysis
• Huge spleen
• Tx:
• FFP: provides the protease but does not eliminate the inhibitor; if not improving, can double the dose
• PET: plasma exchange therapy -- definitive; eliminates the inhibitor
• Steroids, immunosuppressants
• IVIG, antiplatelets = no evidence and antiplatelet increases risk for bleeding
• NO PLATELETS! unless patient is dying from ICH

HUS

• usually kids: 6 mod - 4 years
• Triad: Thrombocytopenia + MAHA + ARF (vs TTP)
• 90% shiga-like toxin E coli 0157:H7
• STEC: endoth damage, thrombin generated, fibrin deposit, platelet-fibrin thrombin
• worsens, do not wax and wane due to fibrin
• high risk Hx: rare hamburger, petting zoo, unpasteurized fruits/juice, unchlorinated water, daycare, long-term care facility
• classic presentation: bacteria ingested (3 days) -> non bloody diarrhea (2 days) -> painful blood diarrhea -> platelet-fibrin clots -> thrombocytopenia, MAHA, ARF
• painful blood diarrhea = usually after FIVE days from ingestion of bacteria
• Dx: Presumptive; Stool for shiga toxin, urine for shiga toxin
• Lab: Thrombocytopenia, Hemolysis (schistocytes, UC bili, LDH, normal fibrin/fibrinogen, negative direct coombs), "negative" blood cultures for E. coli
• Tx: supportive, admission for IVFs, pRBC for Hb <6 or unstable VS, dialysis for anuria, resist urge for platelets (more platelet clots), antibiotics can increase toxin release

HIT: Heparin-induced Thrombocytopenia = BIG CLOTS

• 1-3% of heparin use, can occur with LMWH <1%
• Definition: Platelet <150K; >50% drop from baseline
• Type 1: hours-days
• Type 2: 4-14 days (mean day 9): most common
• Delayed onset: 9-40 days after heparin
• Antibody mediated; Heparin attaches to PF4/platelet factor 4 which initiates immune response
• S/S: Venous thrombosis (more common), Arterial thrombosis (less common), skin lesions, acute reactions, DIC
• Venous: presenting as DVT/PE (heparin underdose or HIT), adrenal thrombosis, cerebral venous/sinus thrombosis, venous limb gangrene
• Arterial thrombosis: limb artery, stroke, MI
• local skin lesions (common in clean): skin necrosis, erythematous plaques
• Diagnosis: 4Ts: Thrombocytopenia, Timing (5-14 days), Thrombosis, no oTher cause = complicated
• Tests: not done in ED, serotonin release assay, HI platelet aggregation assay, etc
• Tx: stop heparin, no platelets, no coumadin until platelet count is normal
• Change to direct thrombin inhibitor: lepirudin, argatroban, bivalirudin
• previous HIT, giving heparin is not c/i (anecdotally no recurrence)

DIC

• sepsis, malignancy, etc
• endothelial damage, systemic release
• Scoring system:
• Tx: cause, suportive

ALGORITHM for low platelet

• isolated low platelet: ITP (self-limiting in kids, in adults = insidious)
• heparin use + big clots: HIT (4Ts): no Heparin, no platelet, DTI
• high PT/INR, microvascular thrombosis, high fibrin/fibrinogen, sick: DIC: give plt
• + MAHA +/- CNS = TTP (waxing and wane, big spleen, plavix)
• + MAHA +/- ARF = HUS (pediatric, does not wax and wane)

Blood Transfusion Reactions

Blood Transfusions (From USC Essentials lecture by Dr Arora)

1. Acute: while transfusion is going on

2. Delayed

WELL ONES

1. Febrile, Non-hemolytic Transfusion Reaction FNHTR

• during or up to 4 hours (therefore, must admit)
• low grade fever, o/w asymptomatic
• cytokine-mediated
• common in old blood products and platelets
• lower in leukocyte reduced products (can give this if patient has recurrent fever during transfusion)
• incidence: 1:5000
• Tx: Paracetamol

2. Simple Allergic (Urticarial) Reaction

• during or a few hours after
• incidence: 1:3-1:300
• if mild (no oral involvement), can continue transfusion
• Tx: Diphenhydramine
• Can premeditate if known hx of same

SICK ONES (MAJOR REACTIONS)

3. Fever, shocky, sick: Acute Hemolytic Transfusion Reaction vs Sepsis

AHTR

• during or up to 4 hours
• true emergency
• incidence: 1:38,000-1:70,000
• mortality: 1:30
• usually ABO incompatibility
• can lead to DIC/shock/ARF
• triad: fever (usually high grade), flank pain, hematuria -- don't wait
• Dx: Pink Plasma, (+) Coombs test: patient's blood send to lab, add Coomb's reagent (antihuman antibodies), if there's antibodies in RBC = agglutinate
• Tx: stop transfusion, recheck patient and blood, notify blood bank, send coombs, T&C, chemistry, Hb
• Tx: supportive (monitor, airway, hemodynamics), 1L NS IV bolus (keep UO >100-200cc/hr), treat HyperKalemia if present

SEPSIS

• usually in first hour
• very rare
• stop transfusion, notify blood blank
• culture blood (recipient and donor blood)
• Broad spectrum antibiotics

4. SOB, uncomfortable

Severe Allergic (Anaphalylactic) Reaction

TRALI (Transfusion-Related Acute Lung Injury)

TACO (Transfusion-Associated Circulatory Overload)

Severe Allergic (Anaphalylactic) Reaction

• usually right at the start, can up to 4 hours
• incidence: 1:20,000-1:50,000
• shock/hypotension/angioedema/respiratory distress
• normal CXR
• Tx: Stop transfusion, supportive, epinephrine (tx as anaphylaxis)

TRALI

• during-4 hours
• 1:5,000-1:150,000 (?)
• pathophys: (not clear): leading theory - HLA antibodies; react with Ag on recipient granulocytes; initiate inflammatory response in the pulmonary vasculature
• more common in female donors (esp with babies cuz they have more HLA antibodies)
• reduced incidence in male donors and females screened for HLA antibodies
• Two-Hit Theory: Patients with underlying systemic inflammation (SIRS/sepsis/trauma/Massive transfusion), likely to get TRALI
• Dx: non cardiogenic pulmonary edema (patchy bilateral alveolar infiltrates); tachypneoa/cardia, hypotension, frothy pink sputum, fever -- well before transfusion
• Tx: Stop transfusion, (NIV), NO lasix (just like non cardiogenic pulmonary edema)

TACO

• during or few hours later
• incidence variable: high in CHF
• symptoms similar with TRALI
• overload: high JVP, Supportive high BP, high BNP
• Tx: stop, supportive, lasix

5. Premedication

Adv: Eliminates minor reactions, patient comfort

Disadv: Masks major reaction, delay treatment

[Volume 48, November 2008, Transfusion]

- n = 315

- placebo vs premed with acetaminophen + diphenhydramine

- no difference in transfusion reactions

ALGORITHM:

1. Suspect acute transfusion reaction?

• Stop
• Recheck Patient and Blood identifiers
• Notify Blood bank

2. If Major/severe: LABS

• Coombs test
• Repeat T&C
• Chemistry
• LDH
• Visual inspection of plasma ?pink
• UA (Hb)
• ?Blood culture

3. 4 Categories (with some overlap)

1. LG fever: FNHTR: antipyretics
2. Isolated Urticaria: Simple Allergic reaction: antihistamines
3. High Fever/Shock: AHTR vs Sepsis: antipyretics, vasopressors, fluids, +/- antibiotics
4. Respiratory distress: Hypotensive (Anaphylaxis vs TRALI), Hypertensive (TACO)

--

Push EM pushemcc+canned.response@gmail.com to me

show details 11:42 PM (2 minutes ago)

Answer Key for PushEM Case of the Week for 9/22/11 - Blood, blood, everywhere...

While consenting a 50-year old man for blood transfusion, you discover that he has had febrile reactions to multiple transfusions in the past, but that these were treated successfully with acetaminophen...

Which of the following products is the best choice to decrease the likelihood of another similar reaction?

a. irradiated packed RBCs

b. leukocyte-reduced packed RBCs

c. regular packed RBCs

d. type-specific packed RBCs

e. whole blood

The answer is B: leukocyte-reduced packed RBCs. Nonhemolytic simple febrile reactions are the most common transfusion reactions and have an incidence of approximately 1%. These are thought to occur from a combination of recipient anti-leukocyte antibodies to transfused cells, and transfused pyrogenic cytokines that accumulate as leukocytes break down. Therefore, administration of leukocyte-reduced packed RBCs can decrease the likelihood of this reaction. Simple febrile reactions can also be prevented and treated with antipyretics. At first, these can resemble more serious transfusion-related reactions such as a hemolytic transfusion reaction and sepsis, which must remain on the differential. Leukocyte-reduced packed RBCs also decrease risk of HIV and CMV transmission and prevent sensitization in patients who might need a bone marrow transplant. Irradiated packed RBCs prevent the capacity of T cells to proliferate and should be considered for neonates and immunocompromised patients, including those with transplants. Whole blood is not as economical as component therapy and is essentially unavailable in the United States; and since it contains WBCs like regular and type-specific packed RBCs, would not be expected to prevent simple febrile reactions.

Hyperleukocytosis and Leukostasis

Hyperleukocytosis is commonly defined as a WBC count in excess of 100,000 per mm3. In acute leukemia, this carries a high early mortality rate of 20–40%. Hyperleukocytosis can cause a leukostasis syndrome. What is leukostasis?

Leukostasis is the accumulation of leukemic blast cells in the capillary lumen ("Ball's Syndrome"), resulting in neurologic and pulmonary manifestations that can lead to intracranial hemorrhage and respiratory failure (JEM, InPress, online 2/23/09)

Tumor Lysis Syndrome

TLS
- massive release of intracellular contents after tumor cell death that can cause seizure and sudden cardiac arrest

Definition by Cairo and Bishop

A. Laboratory TLS (PPCU)
Potassium >6 mEq/L or 25% increase from baseline
Phosphorus >6.5 mg/dL or 25% increase from baseline
Calcium ≤7 mg/dL or 25% increase from baseline
Uric Acid >8 mg/dL or 25% increase from baseline

B. Clinical TLS (Laboratory TLS + the following):
Creatinine ≥1.5x upper limit of normal
Arrythmia or sudden death
Seizure

Oncologic Emergencies

1. TLS (Tumor Lysis Syndrome)
2. Hypercalcemia
3. Hyponatremia and SIADH
4. Adrenal insufficiency

5. Pathologic Fracture
6. Malignant Spinal cord compression
7. Brain Mets
8. Malignant Pericardial Effusion
9. SVC Syndome

10. VTE
11. Hyperviscosity syndrome
12. Hyperleukocytosis and leukostasis
13. Neutropenic Fever

Mayo Clinic Proceedings 2006