Thrombocytopenia in Pregnancy

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Here’s the RoshReview Question of the Week!

A 23-year-old primigravid woman at 25 weeks gestation presents to the prenatal appointment to follow up on lab results. Her platelet count is noted to be 77,000/μL, decreased from 205,000/μL in the first trimester. She reports no abnormal bruising or bleeding. What is the most likely reason for her thrombocytopenia?

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Practice Bulletin 207 is our companion reading this week!

Introduction 

  • Evaluation of thrombocytopenia in pregnancy can be difficult because there are many things that could cause it - not all of them are related to pregnancy 

  • Definition: when platelets are <150,000/microL 

  • So what is normal? 

    • Recall in our very first few episodes that pregnancy can lead to increased plasma volume and not necessarily an equal increase in blood components 

    • This can lead to what appears to be some dilutional effects 

    • In the National Health and Nutrition Examination Survey (NHANES), the mean plt count in pregnancy is as follows: 

      • Non pregnant: 273k 

      • 1st trimester: 251k

      • Second trimester 230k

      • Third trimester 225k 

      • Delivery 217 k 

      • Postpartum (7 weeks) 264k  

  • Definitely suggests that some decrease in platelet count could be expected in pregnancy

What are the causes of thrombocytopenia in pregnancy?

  • Gestational thrombocytopenia - benign and self limited; may even occur in the first trimester, but usually is more common as pregnancy continues; frequency is 5-10% at the time of delivery

    • But remember this is a diagnosis of exclusion! It’s acceptable if there is mild thromboctyopenia, but again, you should look if Plt <100k  

  •  Immune Thrombocytopenia (ITP) - 1-3/10,000 pregnancies, but really low plts only affect a small portion of these

    • ITP is more frequent in pregnancy than in the general adult population but may be because of recognition (checking more frequent CBCs in preg) 

    • Autoimmune condition where antiplatelet antibodies interfere with platelet production and causes destruction of circulating platelets

      • Diagnosis based on exclusion of other causes of thrombocytopenia  

  • Preeclampsia/HELLP Syndrome

    • Remember that it is very rare <24 weeks, and there are usually other signs and symptoms as well like elevated BP, headache, vision changes, etc. As well as other hematologic abnormalities like anemia due to hemolysis (high LDH), and may have abnormal LFTs 

    • We won’t go too much into preeclampsia since we discuss it elsewhere, but always something to keep in mind 

  • Less likely things, but still things to keep in mind 

    • DIC - Disseminated intravascular coagulation

      • There is usually an underlying cause of this such as placental abruption, sepsis, etc 

      • Patients will have bleeding and oozing at IV sites for example 

      • Usually will have low fibrinogen and elevated PT and PTT labs as well  

    • Acute fatty liver of pregnancy 

    • Thrombotic thrombocytopenic purpura (either immune or hereditary)

      • Will usually present with purpura, can have neurological changes, fever, kidney injury, can have elevated BPs and may be confused with PEC 

      • Will have reduced activity of ADMATS13, but this may be a send out lab in most places and will not come back for some time 

      • Will have schistocytes on smear 

    • Lupus 

    • Infection

    • Inherited platelet disorders

So… when should we start to worry?

  • When platelets are: 

    • If platelets are between 100k-150k if there are risk factors present (but usually, do not need work up and can be attributed to gestational thrombocytopenia) 

    • At any point <100k (usually this is beyond the lower end of gestational thrombocytopenia)

      • Plts of <100k only occur in 1% of uncomplicated pregnancies 

      • Remember that there is increased risk of spontaneous bleeding if Plt <20k 

      • Some institutions have cut offs for platelets for ability to give neuraxial analgesia - some places are 70-80k, some places are 100k. Please check with your institution and your patients, because this may require treatment or your patient won’t get an epidural! 

Ok, so that’s a lot of causes… how do I go about figuring out what to do? 

  • Evaluation of the patient

    • Get a good history and physical - this can sometimes help you determine what it is not

      • If patient is well appearing, with no pain, vaginal bleeding, elevated blood pressure or other complaints, it’s usually not going to be something like AFLP, DIC, TTP, or preeclampsia  

      • Look through the patient’s chart: what were their platelets before? What other medical problems? What about new medications? 

      • Any history of lupus, TTP, liver disease, anemia

      • You have the CBC - did the lab do a smear? Are there abnormalities on the smear, like schistocytes? 

      • Most of the time, if you have someone who is sitting in the clinic and appears well, you may have some time  

  • The asymptomatic patient with Plt >100k

    • Usually, plts between 100-150k without other cytopenis or other major clinical findings can be attributed to gestational thrombocytopenia 

    • The other major cause could be ITP, but minor ITP with plt >100k also does not need treatment 

    • Our practice is to check plts monthly to make sure they do not drop below 100k, or below threshold for neuraxial analgesia 

  • The asymptomatic patient with Plt <100k 

    • Review the CBC - make sure there are no other cytopenias; ask for a smear 

    • Evaluate for HIV (usually already done in pregnant patients), as this could also lead to thrombocytopenias 

    • Obtain other coagulation panel like PT, PTT, fibrinogen level 

    • Also obtain CMP - evaluate kidney and liver function 

    • If no obvious signs, it is ok to get hematology involved early

    • More likely to be ITP if <100k, and patients can be treated with steroids or even IVIG in refractory cases if needed 

    • This is to make sure that the platelets do not drop further so that they cannot get neuraxial analgesia or so that they don’t drop too low as to cause issues with bleeding 

  • What if they are symptomatic and <100k?

    • A lot of this is going to depend on their history and physical again - we are usually pretty good at evaluating for preeclampsia - get their vital signs and do your exam

      • Do they have fever? Purpura? 

    • Labs: CBC, CMP, coag panel, HIV, LDH, urinalysis, bilirubin 

    • If you are suspicious of TTP (ie. fevers, kidney injury, neurological changes) 

      • Make sure to get CT head to rule out bleed 

      • ADAMTS13 

      • Hematology consult 

    • Ok to get MFM and hematology involved early 

Management 

  • Treatment for bleeding or severe thrombocytopenia 

    • If Plt are <10k or <20k, there is increased risk of spontaneous bleed 

    • If Plt <20k and severe bleed (ie. intracranial), you should give platelets regardless of the underlying cause of thrombocytopenia (yes, even in ITP if it will get consume)

  • Some platelet thresholds to consider in delivery 

    • Vaginal delivery: 20-30k 

    • C/S: 50k 

    • Neuraxial anesthesia: institution based; ours is 80k; most institutions will have a count between 50-80k 

  • Other considerations 

    • Operative vaginal deliveries are relatively contraindicated if there is severe maternal thrombocytopenia 

    • This is because there is concern that there could also be fetal thrombocytopenia (ie. immune mediated or hereditary) 

    • However, if you must perform an operative delivery, forceps is favored over vacuum 

    • Remember: Just because someone has ITP does not mean they can’t have an operative delivery 

  • Treatment of specific disorders 

    • ITP - steroids or IVIG 

      • Dosing of steroids: prednisone 1mg/kg/day for two weeks followed by gradual taper; may need 2 weeks to see peak effect (usually 1-4 weeks for peak) 

      • IVIG should be given at least 1 week in advance to allow for maximal efficacy and platelet count retesting if trying to raise platelet counts for epidural 

      • If refractory, other methods in pregnancy are not well studied, and you should have a conversation with your MFM and hematology colleagues 

    • TTP - plasma exchange

    • Preeclampsia or DIC due to abruption: delivery! 

  • What about fetal testing of platelets?

    • There isn’t really evidence to suggest we should test fetal platelets (ie. either via PUBS or from fetal scalp during labor

    •  We won’t discuss fetal/neonatal thrombocytopenia here, but just some brief reasons to test neonatal platelets: 

      • Maternal ITP 

      • Neonatal thrombocytopenia in previous pregnancy (concern for NAIT, though this is usually not associated with maternal platelet issues) 

      • Congenital anomalies associated with thrombocytopenia 

      • Bleeding or petechia on the infant 

      • Neonatal infections (ie. CMV, rubella) 

Blood Transfusion

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What’s in blood anyway? 

  • Whole Blood - blood that basically contains all the following components 

    • It contains everything! Most of the time, when we donate blood, we donate whole blood 

  • Red blood cells (often called packed red blood cells) 

  • Take whole blood and centrifuge it to separate out just the red blood cells. Usually, other additives will be placed in such as citrate, dextrose, and adenine to preserve the cells and keep them alive 

    • Usually can be kept refrigerated for up to 42 days in the US, but can be frozen for up to 10 years 

    • Usually 1 unit is from 1 donor, and the idea is that 1 unit should raise the HgB by 1 point 

    • Volume is anywhere between 220-340cc, and the reason this can be different is because it depends on the original HCT of the donor. Most of the time, it is about 250cc.

  • Why do we use it? 

    • Because one needs blood!

      • Should be considered in patients who have acute blood loss anemia, who are symptomatic 

        • Usually can start to think about it if Hgb is <8 g/dL, when not at baseline for patient, and if they are symptomatic 

        • Would recommend if <7 g/dL if they are postpartum or postoperative or wound healing

    • In other cases (ie. sickle cell disease), transfuse to a threshold to prevent sickle crisis 

  • Things to know before transfusion

    • Before transfusion, someone should be typed and crossed so that they get blood that matches their own 

    • If they don’t, their bodies can create antibodies against the donated blood, which can then lead to alloimmunization 

    • This is a problem for future pregnancies possibly! See our episodes on alloimmunization

    • The only exception: massive transfusion or exsanguination protocol when there is no time to type and crossmatch someone 

    • Some people will still have a fever or small allergic reaction to blood - which is why most people are predosed with Tylenol and Benadryl, but we’ll talk more about this in risks/benefits of blood transfusion 

  • Different types of pRBC 

    • Irradiated red cells - indicated for patients at risk of transfusion-associated graft-versus host disease. Components are irradiated by gamma or X-rays within 14 days of donation. Shelf life is about 14 days after irradiation 

    • Washed red cells - for patients who have recurrent or severe allergic reactions to red cells. Also for patients with IgA deficiency with anti-IgA antibodies if red cells from IgA deficient donor is not available. Shelf life is 14 days from washing 

    • CMV negative red cells - only from donors who are known CMV negative. Required for newborn babies because CMV can be fatal 

  • Platelets 

    • How do we get them? 

      • Whole blood donation → centrifuged and the buffy coats (between the red cells and plasma layers are pooled from a few donations to the plasma of one of the donors 

        • Usually, this will result in “pooled platelets” or “platelet packs” so when you transfusion a unit of platelets, it’s actually considered a “4 pack” or “6 pack” or even “10 pack” of platelets. Check with your institution. 

        • Usually, volume is about 300cc, and can be stored at room temperature (20-24 degrees C) with constant agitation 

        • Shelf life is about 5 days 

      • Apharesis donation - platelets come from 1 donor and is apheresed (separated) immediately

        • Will results in only 1 donor per pack of platelets 

        • Volume is around 200cc 

        • Again, can be stored at room temperature with agitation and lasts 5 days 

    • Why do we use it? 

      • Usually when there are low platelets 

      • Most places will have thresholds, ie. if platelets are <50K and patient needs urgent or emergent surgery or are actively bleeding 

      • Some places may put threshold for transfusion of <100k if CNS bleed

      • If not bleeding, generally consider if Plt <10k to prevent spontaneous bleed 

        • If coagulopathy but not bleeding, can consider higher threshold, around 20-30K 

    • Other things to know 

      • Platelets still need to be crossmatched to ABO and Rh antigens 

    • Different types of platelets 

      • Irradiated platelets - same reason to give these as irradiated red cells 

      • Human leucocyte antigen (HLA)-selected platelets 

      • Human platelet antigen (HPA) -selected patients 

        • Population to keep in mind: pregnant patients with neonatal alloimmune thrombocytopenia - where their antibodies attack baby’s platelets 

        • These types of platelets should be used to transfuse babies with NAIT 

  • Plasma (sometimes referred to as fresh-frozen plasma) 

    • How do we get it? 

      • Plasma is from whole blood donation or component donation by apheresis 

      • Usually frozen soon after collection to maintain activity of blood-clotting factors 

      • Can be stored for up to 3 years 

      • Thawed FFP can be stored for 24 hours 

    • Why do we use it? 

      • Contains ALL clotting factors, but the amount will depend on the amount from the donor 

      • Volume of usually 250-300cc 

      • Can be given to patients who have coagulopathy, or whom are bleeding and need massive blood transfusion 

      • Should replace 1:1:1  

  • Cryoprecipitate 

    • How do we get it? 

      • Thawing FFP to about 4 degrees C, which will produce a cryoglobulin rich in fibrinogen, Factor VIII, and von Willebrand Factor. It does NOT contain all clotting factors 

      • Usually single-donor packs or pools 

    • Why do we use it? 

      • Originally developed for treatment of hemophilia

      • It is more concentrated and lower volume than FFP. 1 pack is about 50cc 

      • Consider giving if patient is coagulopathic but also fluid overloaded 

    • Other things about it 

      • Should be stored frozen 

      • Shelf life of about 3 years 

  • Granulocytes 

    • Not going to talk about this one as much, but essentially contains neutrophils 

    • Controversial but sometimes used for patients with life-threatening conditions where they have low neutrophil counts 

  • Human albumin solution 

    • No clotting factors or blood group antibodies, so crossmatching not needed 

  • Clotting factor concentrates 

    • Can be single factor concentrates 

    • Used for treatment of inherited coagulation issues (ie. for hemophilia A, can use recombinant Factor VIIIc) 

    • PCC or prothrombin complex concentrate (PCC) contains factors II, VII, IX, and X. 

  • Immunoglobulin solutions

    • Usually manufactured from large pools of donor plasma

    • Contains antibodies to viruses that are common in the population (ie. IVIG) 

    • Specific immunoglobulins can be made from selected donors with high antibody levels (ie. Anti-D immunoglobulin or Rhogam!) 

Benefits, Risks, and Safety

  • Benefits - and how to safely give blood 

    • As discussed before, blood transfusion can be life saving in many people, but we need to do this safely  

    • We already discussed: type and crossmatch blood 

      • Right patient, right blood, right time → correct patient identification, good documentation and communication, and monitoring of the patient 

      • Patient consent needs to be obtained 

      • Also, do not give more blood than is indicated!  

  • Risks 

    • Mostly morbidity and mortality from blood transfusion is preventable, but can still occur, especially when wrong blood is given 

    • Non-infectious risks

      • Febrile non-hemolytic transfusion reactions (usually mild) - can sometimes be treated with benadryl/Tylenol pretreatment 

      • Allergic reaction - can be mild (ie. urticaria) to severe (angioedema or anaphylaxis) 

      • Acute hemolytic transfusion reaction - usually due to ABO incompatibility 

      • Bacterial contamination of blood - can lead to sepsis 

      • Transfusion-associated circulatory overload (TACO) - worsening pulmonary edema within 6 hours of transfusion 

      • Transfusion-related acute lung injury (TRALI) 

        • Caused by antibodies in donor blood reacting with patient’s neutrophils, monocytes, or pulmonary endothelium 

        • Can lead to leaking of plasma into lung alveolar spaces → cough with frothy sputum, shortness of breath, hypotension, fevers

        • Usually presents within 2 hours of transfusion 

        • CXR will show bilateral nodular shadowing in lungs 

        • Can be confused with acute heart failure, but should not be treated with diuretics 

        • May need to intubate. Supportive care for treatment 

  • What to do about acute reactions? 

    1. Stop the transfusion and undergo rapid assessment of vitals, and make sure to check patient ID and blood ID (does it match?) 

    2. Usual evaluation of ABC (airway, breathing, circulation) 

    3. If mild reactions (ie. isolated temperature of >38 degrees, pruritis, or rash), can consider treatment, but could continue transfusion 

    4. However, if increasing temperature >39, life-threatening changes (ie. allergic reaction with anaphylaxis), stop immediately and proceed to resuscitate as needed 

  • Infectious risks 

    1. Viral infections - risks are incredibly low because every blood donation is screened for HBV, HCV, HIV, HTLV, syphilis, west nile virus, Zika

    2. Every first time donor is tested for Chagas disease 

    3. Creutzfeldt-Jakob Disease - prion disease that first appeared in the UK in 1996. People cannot donate if they have:

      1. Been in UK >3 months from 1980-1996.

      2. Diagnosed with vCJD, or

      3. Had blood transfusion in UK, France, or Ireland from 1980 to present.

What if your patient declines blood transfusions?

  • Respect the values, beliefs, and cultural backgrounds of all patients 

  • Frank discussion with patients about blood transfusion and components of blood 

    • Jehovah’s Witness patients usually will refuse transfusion of whole blood and primary blood components (ie. red cells, platelets, white cells, and plasma) 

    • However, some may accept derivatives of primary blood components (ie. albumin, cryo, clotting factors, immunoglobulins) 

  • Discussion of how to save blood cells and discuss other methods of decreasing likelihood of transfusion 

    • Intraoperative cell saver, apheres, dialysis, or cardiac bypass are usually ok 

    • Iron transfusions if needed prior to procedures, if there is time 

    • Discussion of autologous transfusion if possible 

  • Signing advance decision documents (usually most hospital will have these) about which blood products are acceptable and which are not 

  • Remember: 

    • Emergency or critically ill patients with temporary incapacity must be given life-saving treatment (including blood transfusion) unless there is clear evidence of prior refusal