Best Practice for Platelet and Plasma Transfusion

Nicole Draper, MD

Platelets

Platelet Storage and QC

• Whole-blood derived or apheresis

• 5 days at 20-24 oC– Temp needs to be maintained in transport,

while held in OR or ICU etc.

• Gently agitated

• Stored in plasma or additive solution

• Must test for bacterial contamination

• Must have >3.0 x 10 11 platelets per apheresis unit

Case 1

• 30-year-old woman with h/o tetralogy of Fallot with cadaveric pulmonic valve, ASD closure device.

• Admitted with right heart failure found to have pulmonic valve vegetations complicated by severe pulmonic regurgitation.

• OR tomorrow for redo pulmonary valve replacement

• Cardiac bypass pump

Platelet Transfusion Indications

• Prophylaxis– Non-bleeding patients– Platelet count <10x109/L

• Treatment– Bleeding/surgical patient– Platelet count <50x109/L typically– Neurological often <100x109/L– Platelet dysfunction (aspirin, clopidogrel,

uremia, plastic, pumps, congenital)

Hgb 6.8 (11-16g/dL)Plt 146 (150-400x109/L)ACT 353 (74-137sec)PT 23.8 (11.4-14.4 sec)Fibrinogen 129 (150-400mg/dL)Actively bleeding

Platelet Count and Bleeding

Harker LA, Slichter SJ. N Engl J Med 1972;287:156 Slichter SJ. Transfus Med Rev. 2004 Jul;18(3):153-67

Often platelets will not stop bleeding, but need to prevent levels so low as to have additional spontaneous bleeding

Platelet Count and Bleeding

http://imaging.ubmmedica.com/cancernetwork/journals/oncology/images/o0009sup8cf2.gif

Platlet Count and Procedures

McVay PA, Toy PT. Transfusion 1991;31(2):164-71.

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Platelet Count and Procedures

• PTs and PTTs 1.1-1.5 times midrange normal levels and platelet counts 50-99 x 10(9)/L.

• Percutaneous liver biopsy 177 inpatient procedures (155 standard, 22 fine needle).

• Bleeding complications in patients with platelet counts greater than or equal to 50 x 10(9)/L was 3.4% (6 of 175), with no significant difference from patients with normal parameters.

• Highly associated with bleeding complications: a patient diagnosis of malignancy, 14% (7 of 50) compared with 0.8% (1 of 127) among other patients (P less than 0.001).

McVay PA, Toy PT. Am J Clin Pathol 1990;94(6):747-53.

Platelet Dysfunction: Aspirin

Figure 2 . Before and after transfusion platelet function assay results without change in platelet function.

Figure 3 . Before and after transfusion platelet function assay results with change in platelet function.

No difference in the progression of ICH (37.5% vs. 30%, p = 0.7), neurosurgical intervention (12.5% vs. 15%, p = 0.8), and platelet count (240.9 vs. 252.1 p = 0.32)Joseph B, Pandit V, Sadoun M, Larkins CG, Kulvatunyou N, Tang A, et al. J Trauma

Acute Care Surg. 2013;75(6):990-4.

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Platelet Dysfunction: Uremia

TMRE

PS Exposure

Enhanced platelet apoptosis in chronic uremic patients.2014 Mar 24.

Platelet Dysfunction: CPB• Several studies have found that laboratory

predictors of platelet dysfunction do not significantly correlate with bleeding after CPB.

• There is a clear correlation between the duration of CPB and the BMI with blood loss.

Perioperative monitoring of primary and secondary hemostasis in coronary artery bypass grafting. Semin Thromb Hemost. 2005;31(4):426-40.

Platelet Transfusion Contraindications

• Nonbleeding patients on antiplatelet medications or with platelet dysfunction extrinsic to the platelet (uremia, von Willebrand disease)

• Activation or autoimmune destruction of endogenous platelets (HIT, TTP, ITP) unless there is life-threatening hemorrhage

Blood Samples• Two unique patient identifiers

• Zero-tolerance for clerical errors– Most common cause of fatal hemolytic

transfusion reactions

• New sample every 3 days required if– Pregnant or transfused RBCs in the past 3 months– Usually a universally applied

criteria for RBCs

• Platelets and plasma often transfused on historical blood type

Platelet Compatibility

• Weak ABO antigens on platelets

• 20-40% reduction in count increase if incompatible– Care more about the ABO antibodies in the plasma

that can hemolyze red cells– Soluble A or B antigenic substance in pt plasma

• Type-A donors recruited to apheresis platelets

• Type-O donors recruited to RBC donation

Question 1

An Rh+ platelet is transfused to an Rh- patient. Which of the following does the patient need?

A. RhIg regardless of age and sex

B. RhIg if female with childbearing potential

C. No administration of RhIg

Rh Compatibility

Recipient RBC Plasma Platelets

Rh- Rh- Rh-, Rh+ Rh-, (Rh+)

Rh+ Rh-, Rh+ Rh-, Rh+ Rh-, Rh+

• Anti-D not naturally occurring in plasma• No Rh(D)-antigen on platelets• Possible red cell contamination of platelets

– As little as 1 mL of blood in a liter of plasma is visually pink/red

– <0.001 mL RBC in an apheresis platelet unit– Tenths of a mL in pooled WB derived platelets

RhIg and Platelets• Anti-D alloimmunization after

D-incompatible platelet transfusions: a 14-year single-institution retrospective review at Beth Israel Deaconess Medical Center.

• Of 130 eligible D− patients, 48% women and 57% immunocompetent, who received a total of 565 apheresis PLTs, none formed anti-D.

28%

Transfusion. 2014 Mar;54(3):650-4.

Platelet Dosage and Effect

• Whole-blood-derived platelets and apheresis platelets have equivalent efficacy

• Dose– 1 apheresis platelet– 6-pack of whole blood platelets– 5-10 mL/kg in pediatric patients• Increase by 30-60 x 109/L in 70 kg adult• Typical life-span of 3-4 days post transfusion

Platelet Refractory• Unresponsive to platelet transfusion

– Immune or nonimmune? 10-60 minute post-transfusion count

• Nonimmune causes– Splenomegaly– Fever– Sepsis– Bleeding– DIC/Mechanical– Drug

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Immune

Nonimmune

Platelet Refractory

• Platelet alloantibodies: Anti-HLA class I or platelet-specific antibodies– Previous transfusion or transplantation– Pregnancy– Recipient dependent, not dose

• Treatment: HLA-matched or crossmatched platelets

• Prevention: Leukocyte reduction

Case 2

50-year-old woman with suspected aplastic anemia

Pre Plt Count Post Plt Count

2/21 1830 5 2030 3

2/22 0030 3 0130 4

2/22 1030 4 1400 4

Platelet Refractory: PRA

HLA-Matched Platelets

Apheresis Platelet Unit

Case 250-year-old woman with suspected

aplastic anemiaPre Plt Count Post

Plt Count

2/21 1830 5 2030 3

2/22 0030 3 0130 4

2/22 1030 4 1400 4

2/28 1230 3 1330 50

3/1 1300 27

3/2 1800 22 2100 56

Plasma

Plasma

Volume: 200 – 600 mL

Content: PlasmaAnticoagulant

PLASMA250 mL

200 mL

300 mL

500 mL

600 mL

==INR = 1.3

Plasma Types

• Fresh Frozen Plasma (FFP): frozen within 8 hours of collection

• Plasma Frozen within 24 Hours (PF24): frozen within 24 hours of collection

• Thawed Plasma (TP): derived from FFP or FP24 and maintained for a maximum of 5 days after the day of thaw

• Plasma Cryoprecipitate Reduced: low levels of fibrinogen, FVIII, vWF, FXIII, fibronectin

Stored frozen < -18°C

FFP FFP,Thawed

>24 h

ThawedPlasma

(up to 5 days after thawing)

Handling Options for FFP

Thawed at30-37ºC

Store at1-6ºC

Transfuse

Coagulation Factor Activity of Thawed

PlasmaDay 1 Day 2 Day 3 Day 4 Day 5 % change

Day 1 to 5 p

Fibr 225 224 224 224 225 0 NS

II 81 81 81 80 80 1 NS

V 79 75 71 68 66 16 NS

VII 90 81 76 72 72 20 NS

VIII 107 76 66 65 65 41 <.02

X 85 84 84 82 80 6 NS

Downes K et al. Transfusion 2001;41:570

Tabular entries as % activity NS = not statistically significant

Question 2

All of the following are preferred uses of fresh frozen plasma except?

A. Massive transfusion

B. Reversal of warfarin anticoagulation

C. Treatment of hemophilia A

D. Treatment of TTP

Plasma Transfusion Indications

• Bleeding or preoperative patients– Deficiency of multiple coagulation factors

• liver disease• warfarin therapy• massive transfusion • disseminated intravascular coagulation

– Specific factor deficiency, no concentrate

• Thrombotic thrombocytopenic purpura

• Rare specific plasma protein deficiency

Contraindications

• When a coagulopathy can be corrected more effectively with a specific therapy– Vitamin K– Cryoprecipitated AHF– Prothrombin complex concentrates

• When blood volume can be safely and adequately replaced with other volume expanders

Plasma Dosage and Effect

• The volume transfused depends on the clinical situation and patient size

• May be guided by laboratory assays of coagulation function

• No QC for plasma products

PLASMAPLASMA

USUAL DOSE FOR CONTROLOF BLEEDING: 10-20 mL/kg

Plasma Dosage and Effect

DeterminantsPatient sizeBleeding siteFactor activity: Initial, targetFactor concentration in plasma Factor half-life in vivoUnit volumeRx: 2 units??

Hgb 6.8 (11-16)Plt 146 (150-400L)ACT 353 (74-137)PT 23.8 (11.4-14.4)Fibrinogen 129 (150-400)Actively bleeding

70 kg x 15mL/kg x 1unit/250ml = 4.2 4 units

Edmunds LH. Hemostasis and thrombosis: basic principles and clinical practice. 4th ed. 2001 p1031-43

Abnormalities in Coagulation Testing

do not Necessarily Indicate a Clinical Coagulopathy

Normal HemostaticFibrinogen 200-400mg/dL 50-100mg/dLFactor V 1 U/mL 5-25%Factor VII 1 U/mL 5-25%Factor VIII 1 U/mL 5-25%

Normal concentration: 1 U/mL = 100% activity

Mild elevations of PT, INR, aPTT overestimate clinical benefit of

transfusing plasma for patients in most clinical situations.

1.3 x upper limit of reference range (in seconds) - or –

1.5 x midpoint of reference range (in seconds))-McVay PA et al. AJCP 1990;94:737-53.-McVay PA et al. Transfusion 1991;31:164-71.-Counts RB et al. Ann Surg 1979; 190:91-9.-Ciavarella D et al. Br J Haematol 1987;67:365-8.-Auble T et al. Acad Emerg Med 2002;567-574-Stanworth SJ, Hematology Am Soc Hematol Educ Program 2007:179-86

Generally recommended transfusion trigger points in appropriate situations:

Using Screening Tests to Predict Plasma Need

Prophylactic Plasma Transfusion

Almost no effect with an INR <1.85

Holland LL, Brooks JP Am J Clin Pathol. 2006 Jul;126(1):133-9. Abdel-Wahab OI, Healy B, Dzik WH Transfusion. 2006 Aug;46(8):1279-85

Patients receiving FFP and having pretransfusion and posttransfusion PT/INR. Patients with acute trauma, in the operating room, with excessive factor consumption (ie, DIC), or given PCC were excluded.

Plasma Transfusion for Invasive Procedures

Segal JB, Dzik WH. Transfusion 2005;45:1413-25 http://onlinelibrary.wiley.com/doi/10.1111/j.1537-2995.2005.00546.x/full

Technical skill of the person performing the procedure inversely correlates with bleeding

Thrombelastography (TEG)

• In 76 patients, routine coagulation tests (i.e. prothrombin time, fibrinogen level, d-dimer, and platelet count), thrombelastography, and whole blood aggregometry were obtained perioperatively and on days 1 and 3 after OPCAB.

• Intra- and postoperative blood loss was determined

Poston R et al. Eur J Cardiothorac Surg 2005;27:584-591

Poston R et al. Eur J Cardiothorac Surg 2005;27:584-591

Significant correlation with 24h hemoglobin loss was seen only with a perioperative decline in the maximum amplitude of the TEG trace (R=0.45,

P 0.05) and fibrinogen levels (≪ R=0.43, P 0.05).≪

TEG

TEG

Perioperative monitoring of primary and secondary hemostasis in coronary artery bypass grafting. Semin Thromb Hemost. 2005;31(4):426-40.

Effect of Body Temperature on Coagulant Activity

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37 34 31 28

PTT

PT

oC

Sec

on

ds

Rohrer MJ, Natale AM. Crit Care Med 1992;20:1402-5

© 2003 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc.

Meng ZH et al. J Trauma 2003;55:886-91

Effect of Acid/Base Balance on Coagulant Activity

Question 356-year-old woman with ESLD secondary to hepatitis C is reported to have sudden onset respiratory distress at approximately 10:30am. Intubated at 11am. She was scheduled for a procedure in IR and received 6 units FFP from 5am to 10am.

  Time Hb INR T Bili Haptoglobin

0400 8.6 2.5 3.7

1130 6.9 1.9 4.1 17.0 (41–165)

A. Hemolysis

B. Fluid overload

C. TRALI

D. Bacterial contamination

At the Bedside• Clerical check• Visual check• 170-260µ filter removes fibrin

clots, aggregates• 22-14 gauge needle/catheter

– 24 for pediatric if necessary

• 0.9% (normal) saline• Appropriate blood warmers• Transfusion must be completed within 4 hrs• Stop transfusion if suspect reaction

Blood is a Drug

• The blood bank is the only part of the laboratory that is regulated by the FDA

– Blood products are biologic drugs

– Lab + pharmacy

• Include transfusion history as part of a drug history

Possible Side Effects

• More likely with massive transfusion– Hypothermia

– Hyperkalemia

– Metabolic acidosis (citric acid)

– Hypocalcemia, hypomagnesemia

Infectious Disease Transmission

• Infectious Disease Testing– HIV: anti-HIV-1/2, HIV RNA (1:1.5 million)– HCV: anti-HCV, HCV RNA (1:1.2 million)– HBV: HBsAg, anti-HBc, (1:280,000)– HTLV: anti-HTLV-I/II– WNV: WNV RNA– Syphilis: anti-Treponema pallidum– Chagas: based on history– CMV: optional

Types of Transfusion Reactions• Fever

– Febrile– Hemolytic (delayed vs. acute)– Bacterial sepsis

• Respiratory distress– Transfusion related acute lung injury (TRALI)– Transfusion associated circulatory overload (TACO)– Allergic (anaphylaxis)

• Rash ● Thrombocytopenia– Allergic – Posttransfusion purpura– TA-GVHD – Platelet refractory

References

• Transfusion therapy: clinical principles and practice / editor, Paul D Mintz. 3rd ed. AABB 2011.

• Technical manual / editor John D. Roback. 17th ed. AABB 2011.

• Circular of information for the use of human blood and blood components. http://www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/guidances/blood/ucm364565.htm

Questions