Platelet Transfusions

Ira Shulman, MD

Background:

• Close to 3 million platelet transfusions in the U.S. every year

• “Single donor” platelets (apharesis platelets) used at LAC-USC rather than the former “six pack” (pooled platelet concentrates) to reduce infection risks

Transfusion Guidelines:

• Platelet transfusion guidelines to treat bleeding or to prevent bleeding in thrombocytopenia

• Expected rise in platelet count after transfusion is based on weight

70kg (150lb) – 1 apharesis pack (450 billion platelets) à expected increase ~ 30,000

More if a smaller patient, less if a larger patient (may require 2 apharesis packs)

Post-count should be obtained 30 minutes after transfusion

May be blunted by DIC, SIRS, or other inflammatory responses

• ABO compatibility

Typing of platelets isn’t necessary for transfusion, however:

Compatibility improves incremental rise in platelet counts & long-term outcome

• Platelet transfusion NOT recommended in:

ITP (Idiopathic thrombocytopenic purpura) – not recommended unless actively, significantly bleeding.

Autoantibody will destroy transfused platelets. Massive transfusion may be a temporizing measure.

PTP (Post-transfusion purpura) – Rare condition caused by autoantibody formed in females days after PRBC transfusion.

Platelet counts drop. Treatment is IVIG. Transfusion of platelets not indicated as counts will improve.

HIT (Heparin induced thrombocytopenia) – Caused by antibody formed against heparin-platelet factor IV complex. Platelets

may actually increase risk of thrombotic event.

TTP (Thrombotic thrombocytopenic purpura) – platelets may increase microthrombotic event.

Risks of platelet transfusion:

• Platelet transfusions are discouraged because of limited resources & other risks

Riskiest blood product transfused

• TRALI (Transfusion Related Acute Lung Injury)

Acute onset of respiratory failure with hypoxemia; higher risk in SIRS/sepsis

CXR: bilateral infiltrates, haziness

#1 cause of transfusion death

1 in 5,000 transfusions, 5% death rate

TRALI theories:

Donor has anti-HLA antibodies in plasma at time of donation à recipient with same antigen on WBCs. As blood products are stored, bioactive lipids are released & activate neutrophils on capillary endothelium

TRALI is most associated with apharesis platelet transfusion from female donors

Male blood products are safer because less WBC antibodies formed

Hemostatic Resuscitation

• LAC-USC data: Patients requiring >10 units PRBC in 12hrs, aggressive plasma & platelet support have better outcomes

• However, if patients require < 10 units PRBC in 12-24hrs, plasma & platelet transfusion may cause more harm (higher risk of ARDS & complications) and no gain in outcomes

• What if you don’t know?

If patient on anti-coagulation, begin with aggressive plasma/platelet transfusion

If not, after 6 units PRBC given à move on to plasma/platelet transfusion

Up to 25% of massively injured trauma victims are already coagulopathic by the time they reach the ED (due to activation of

thrombin, Protein C & massive fibrinolysis)

ANAPHYLAXIS:

Epidemiology

• Incidence- likely under-reported because no set definition

Pathophysiology

• Sensitization-exposure leads to Ig-E antibodies on mast

cells and basophils

• Re-exposure-cross-linking of antibodies causes release of

active mediators

⇒ Histamine, cytokines, leukotrienes…

Classification

• Gell-Coombs classification

⇒ See Chart (Am Fam Physician 2003;68:1781-90)

• Anaphylactoid reaction

⇒ Immediate systemic reaction that mimics anaphylaxis but→ no Ig-E antibodies

⇒ Can occur on first exposure

⇒ Reactions dependent on systemic exposure

⇒ Example: radiographic contrast

⇒ Acute treatment similar to true anaphylaxis

Clinical Symptoms (4 organ sx)

• Respiratory-upper or lower

• Cardiovascular-entire spectrum

• Gastrointestinal- N/V/D, wide variety sx

• Skin-we associate with anaphylaxis but skin findings absent 10%

Definition

• No good definition→we know it when we see it

• Spectrum

⇒ Urticaria, Angioedema

√ versus non-specific rash?

⇒ Anaphylaxis (at least 1 out of 2: )

√ Respiratory difficulty→throat, posterior pharynx, larynx

√ Hemodynamic instability

Etiology

• Foods→most common

⇒ Early life: allergens that are outgrown (eggs, milk, soy)

⇒ Later life: peanuts, treenuts, fish, shellfish

√ If these occur in early life→ tend to not outgrow

• Medications→antimicrobials, NSAIDS, ASA, any

• Exercise induced→ ½ are food induced

• Idiopathic→20%

• Other→Hymenoptera, latex, blood components, beer, others

Differential diagnoses

• Scombroid poisoning: 30 min after spoiled fish (tuna, mackerel, mahi-mahi), N/V/D, urticaria

⇒ Treatment→antihistamines

• Angioedema:

⇒ Hereditary→C1 esterase inhibitor replacement, FFP; (not associated with urticaria)

⇒ ACE-inhibitor induced→ manage airway + usual treatment

• Severe Asthma

• Panic disorders

Treatment Recommendations (J Allerg Clin Immunol 2005;115:S483-523)

• Oxygen

• IV Fluids

• Epinephrine (1st line agent)

⇒ Route

√ IV→ virtually all adverse outcomes in literature are from IV use

i ↑adverse effects when given too rapidly, too concentrated, or too high of a dose

ii Reserve for sickest patients (true shock, not responsive to IM)

√ IM vs SQ→ more rapid peak plasma concentrations with IM use in children and adults

i Adults-J Allergy Clin Immunol. 2001;108:871– 873;   Children: J Allerg Clin Immunol 1998;101:33

ii SQ absorption decreased in shock states

iii Epinephrine is vasoconstrictor→ decreases its own absorption

iv Limitations of recommendations→need study with both injections in thigh, studies done with

patient not in anaphylaxis

√ Recommendations: IM is better than SQ, regardless of age

⇒ Dose

√ IM Dose

i Adults IM: 0.3-0.5 mg IM of 1:1000 repeat q 5-15 min

ii Pediatrics IM: 0.01 mg/kg to max 0.3 mg 1:1000 IM repeat q 5-15 min

√ IV Dose: 0.1mg IV = 100 mcg IV = 1ml of 1:10,000 (need to dilute to 10 or

100ml→see below!)

i Dilution options: go to http://emrap.tv/

(a) Option #1: add 1ml of 1:10,000 solution to 9ml NS →10 ml of

1:100,000 dilution (10mcg/ml) over 5-10 min →10-20mcg/min

(b) Option #2: add 1ml of 1:10,000 (crash cart epi) to 100ml NS and run

over 5-10min→ (1mcg/ml) = 10mcg/min

(c) Compare to epinephrine gtt→1-4 mcg/min

(d) Pediatrics: 0.1mcg/kg/min (diluted to 1:100,000 solution) and titrate to

response

√ Epinephrine gtt: same dilution as option #2→(1mcg/ml), to run at 1-4

ml/min (1-4 mcg/min)

⇒ Safety?

√ IV→ virtually all adverse outcomes in literature are from IV use

√ IM/SQ→not too bad

√ Caution: elderly, hypertensive, CAD

⇒ Contraindications?

√ No absolute contraindications

√ β –blockers:

i Anaphylaxis may be worse

(a) relative state of hypoadrenergic;

(b) β –receptors are blocked (Epi won’t work on β receptors→unopposed α blockade)

ii Recommendations:

(a) ½ dose of epinephrine→ evaluate for response

(b) Glucagon (bypass β receptor altogether→ still stimulates cAMP)

(i) Dose: Glucagon 1-2 mg IV q 5-10min

(ii) Adverse effects: Nausea/Vomiting

√ Epinephrine allergy

i Not true allergy, likely preservative allergy→ MBS, sulfite

ii Recommendation: Sulfite-free epinephrine?

• Antihistamines (2nd line agent)

⇒ H1 blockers

√ Diphenhydramine→works well, can give IV

√ Non-sedating H1 blockers?→not available for IV use

⇒ H2 blockers

√ Benefit over H1 blockers alone

√ Low adverse effects (except possibly cimetidine→CYP450)

• Corticosteroids

⇒ Delayed effect of corticosteroids?

⇒ May prevent recurrent anaphylaxis

⇒ No role in acute management?? (J Allerg Clin Immunol 2005;115:S483-523)

⇒ Effects never been validated in placebo controlled studies, effects extrapolated from asthma

• Inhaled β2 agonist (albuterol)→if bronchospasm

• Remove source: venom sac! Stop antibiotics

• Vasopressin?

• AHA Summary of treatment recommendations (Circulation 2005;112;IV-143-IV-145)

⇒ Click on this: http://circ.ahajournals.org/cgi/content/full/112/24_suppl/IV-143

• Special Case: Cardiac Arrest

⇒ Aggressive fluid resuscitation (4-8L)

⇒ High dose epinephrine IV: 1mg→3mg→5mg then start infusion at 4-10mcg/min

⇒ Antihistamine IV

⇒ Steroids IV

⇒ Prolonged CPR→effective CPR may maintain O2 delivery until catastrophic effects of anaphylaxis resolve

• Airway management

⇒ RSI normal way vs

⇒ Supraglottic device (LMA, Combitube)→less increasing edema without endotracheal tube in?

⇒ Angioedema ?→ consider nasotracheal intubation (prepare for cric)

Disposition

• Mild Urticaria (no respiratory compromise/hemodynamic instability)→Home

• Severe anaphylaxis (intubated, epinephrine gtt)→ICU

• Anaphylaxis that improves?

⇒ Recurrent anaphylaxis?

√ Biphasic or multiphasic form of anaphylaxis

√ Reappearance of allergic phenomenon after resolution of original symptoms

√ As high as 20% and as long as 72 hours after initial event! (see chart below)

√ Hong Kong study (Journal of Emergency Medicine, Vol. 28, No. 4, pp. 381–388, 2005)

i Biphasic symptoms in 5% of 282 patients

ii 3 patients with stable VS on presentation→ developed hypotension or severe dyspnea on

recurrence

√ Corticosteroids do not prevent this phase from recurring

⇒ Observation?→ no firm established criteria

√ Mild sx→ several hours, 4hours

√ Severe sx → observe x 24hours or admit

⇒ High risk features for fatal anaphylaxis

√ Specific allergens: peanuts, treenuts

√ H/O Asthma

• Discharge planning

√ Reliable caretaker?

√ Access to 911?

√ H1/H2 blocker

√ Corticosteroids x 3-5 days

√ Self-injectable epinephrine

i Underprescribed→ should be given to all true anaphylaxis,

maybe multiple

ii EpiPen and EpiPen Jr

iii Twinject→can administer 2 doses

iv Education: YouTube?

Adverse Drug Reactions

• Define: All non-therapeutic consequences of drug, excluding treatment failure, poisonings or drug abuse.

• Allergic ADRs: 5-25% of ADRs

⇒ Type 1 Hypersensitivity→ small fraction of allergic ADRs

⇒ Is patient having a true ADR?

• Non-allergic ADRs: N/V/D, weakness, non-specific rash (urticaria vs routine maculopapular eruption)???