Labs and Quiz

The following is the patient’s complete blood count (CBC):

What’s what: WBC, white blood cell count; Hb, hemoglobin; MCV, mean cell volume; MCHC, mean cellular hemoglobin concentration; RDW, red cell distribution width; platelets, PLT; Normal values: WBC 5-10 x 10⁹/L, RBC 4-6 x 10¹²/L, Hb 12-16 g/dL, Hct 35-47%, MCV 80-100 fL, MCHC 32-36 g/dL, RDW-SD < 45%, platelets (PLT) 150-450 x 10⁹/L

Her coags are:

What’s what: PT, prothrombin time; INR, international ratio; aPTT, activated partial thromboplastin time; Normal values: PT 9.1-12 seconds, aPTT 24-33 seconds, fibrinogen 230-510 mg/dL.

Question 1: . Based on the information provided, what is appropriate for this patient:

Explanation to question 1:

The correct answer is D (transfuse one RBC and one cryoprecipitate dose).

Indications for transfusion are based on most current guidelines.¹ Because this patient is bleeding, tachycardic and has a Hb level below 8 g/dL, RBC transfusion is indicated. One RBC unit should be transfused followed by reassessment.

While transfusion of plasma appears to be indicated as he is coagulopathic likely due to liver insufficiency, based on the laboratory data he would benefit from transfusion of cryoprecipitate as his fibrinogen levels is below 100 mg/dL. Lack of fibrinogen is likely the cause for his bleeding and increased PT/aPTT, therefore correction of this parameter should improve his clinical status. Plasma, cryoprecipitate and fibrinogen concentrate all contain fibrinogen, however, only cryoprecipitate and fibrinogen concentrate are low-volume options.

Unlike, the fibrinogen concentrate, cryoprecipitate requires thawing. Cryoprecipitate, also called cryoprecipitated antihemophilic factor (CAH), is indicated in clinical conditions associated with bleeding due to low fibrinogen such as:²

• Liver transplant/insufficiency
• Postpartum hemorrhage
• Cardiac surgery associated with acquired deficient hemostasis

Other indications for cryoprecipitate are:

• Factor XIII deficiency – when recombinant (Tretten) or plasma-derived FXIII (Corifact) are not available
• Uremia (although data supporting this indication are debatable).

There is insufficient evidence regarding the threshold of fibrinogen level or the optimal dosage for patients with hypofibrinogenemia undergoing procedures. However, it’s recommended to use a trigger of < 100 mg/dL in patients who are bleeding or who are at high risk for bleeding and < 200 mg/dL in unstable patients with rapid ongoing consumptive coagulopathy such as obstetric or hematology-oncology patients with active DIC, cardiac surgery patients, patients with bleeding complications following tPA infusion [1,2].³ The approval for this product should be done without waiting for results of lab tests.

Question 2: Which of the following is/are true about cryoprecipitate (more than one answer may apply):

Explanation to question 2:

The correct answer is C (cryoprecipitate contains: Fibrinogen, factor VIII, factor XIII, von Willebrand factor, and fibronectin).

Answer 1 is not correct: cryoprecipitate is made from thawing (not freezing) FFP at 1-6C to a slushy state which leads to precipitation of cold-insoluble HMW proteins followed by centrifugation to express plasma (cryo-poor plasma). A single cryoprecipitate unit of ~15 mL-20 mL is obtained after thawing one FFP unit. The cryoprecipitate is refrozen within 1 hour and it has a shelf life of 1 year frozen at ≤ -18^oC.

Answer 2 is incomplete. One cryoprecipitate unit contains:

• Fibrinogen (~250 mg)
• Factor VIII (~80-120 IU)
• Factor XIII (~ 60 IU)
• vWF (~ 170 IU)
• Fibronectin

Answer 4 is partially incorrect: cryoprecipitate is stored 1 year frozen at ≤ -18^oC, and 6 hours after thawing. When ready for transfusion, it is thawed at 30-37^oC and after thawing is kept at 20-24^oC for 6 hours. It should not be refrigerated after thawing. If pre-pooled, it expires in 6 hours after pooling in a closed system using sterile connection device or 4 hours after pooling in open system.⁴

Question 3: What is the right dosage for fibrinogen for this patient knowing that his weight is 70 kg:

Explanation to question 3:

The correct answer is C (10 cryoprecipitate bags)

The starting therapy for an adult is in general one dose. This is equivalent of 10 units or 10 bags. Children should be transfused with 1-2 bags/10 Kg and neonates with 1 bag.

The exact fibrinogen dosage is calculated based on the following formula: Number of cryoprecipitate units needed = (Desired fibrinogen increment x PV)/250, where the desired fibrinogen increment is the difference between the desired fibrinogen level and the current fibrinogen level, and the PV is the plasma volume calculated as (1-Hct) x TBV (total blood volume). 250 represents the amount of fibrinogen per cryoprecipitate bag.

For this particular patient, the TBV is 70 mL x 70 Kg = 4900 mL= 49 dL Fibrinogen units = [(100-40 mg/dL) x (1-0.23) x 49 dL]/250 mg= (60 x 37.73)/250 = 9.05 units.

Question 4: Which of the following is not available as a pathogen-reduced component:

Explanation to question 4:

The correct answers is A.

Products currently approved by FDA for pathogen reduction (PR) technology include:⁵

• Apheresis platelets
• Whole-blood-derived plasma
• Apheresis plasma:
  • Pathogen Reduced, Cryoprecipitated Fibrinogen Complex (PR CFC)
  • Pathogen Reduced Plasma, Cryo- precipitate Reduced (PR PCR)

Pathogen reduction is an ex-vivo process used to eliminate microorganisms and reduce transfusion-transmitted infection (TTI) risk, including sepsis; it is also used as an alternative to irradiation to prevent transfusion-associated graft versus host disease (TA-GVHD). PR technology has been shown to also inactivate residual lymphocytes.

PR requires ex vivo processing by addition of a light sensitive chemical (amotosalen) to the blood component followed by UVA exposure and chemical residue removal.

Unlike cryoprecipitate, the PR CFC has a 5-day post-thaw shelf life. Like cryoprecipitate, it is indicated for bleeding due to fibrinogen deficiency, bleeding when recombinant and/or specific virally inactivated preparations of Factor XIII or von Willebrand factor are not available, as a second-line therapy for von Willebrand disease, and in uremic bleeding if other therapies failed. Due to its extended shelf-life and unlike cryoprecipitate, PR CFC is cannot be given as for replacement of Factor VIII. It is also contraindicated in patients with hypersensitivity reaction to amotosalen or other psoralens and neonatal patients treated with phototherapy devices.  In this latter category of patients there is a risk of developing erythema due to from interaction between ultraviolet light and amotosalen present in the pathogen-reduced blood components.⁶ 

Is compatibility testing required before transfusion of cryoprecipitate?