POSTOPERATIVE THROMBOCYTOPENIA

Background

• Commonly encountered hematologic abnormality after major surgery, although actual incidence not reported in literature. (Ref 1)
• Defined as platelet count <150K.  Generally, platelets>50K are not associated with significant bleeding.  Spontaneous bleeding usually does not occur with platelets >20K. (Ref 2)

Evaluation:

• History:  Review medications, transfusion history, symptoms of infection, symptoms/history of liver disease.
• Exam:  Assess for infection, splenomegaly, signs of liver disease, evidence of thrombosis

Differential diagnosis
Degree of thrombocytopenia is useful in helping determine etiology

Platelet Decrease	Etiology	Description
Mild-Moderate	Consumption	Seen in larger blood loss surgeries. Occurs immediately after surgery. Returns toward normal within 2-3 days.
	Thrombocytopenia due to infection	Associated with both viral and bacterial infections. In severe cases, part of disseminated intravascular coagulation (DIC). Other mechanisms less well understood. (Ref 1)
	Pseudo-thrombocytopenia	Artifact due to EDTA in CBC tube.  Clumping present on smear.  Re-draw platelet count in tube containing citrate instead of EDTA.
	Heparin Induced Thrombocytopenia	HIT—see below.
	Post transfusion thrombocytopenia	Occurs soon after transfusion (may be after surgery if transfusions given during case). Severity tends to be proportional to the volume of blood administered.  Clinical course usually benign. Platelet count usually returns to normal within 3-5 days after blood transfusion. (Ref 1)
Severe	Drug induced Immune thrombocytopenia	Quinidine, digoxin, alpha methyl dopa, penicillin class drugs, thiazides, septra, cimetidine, famotidine. Platelet count is often extremely low (can be less than 20,0000).   Can cause postop bleeding.  Platelet transfusions useful. Steroids not shown to be useful. (Ref 1)
	Post transfusion purpura	Acute thrombocytopenia caused by alloimmunization against transfused platelets occurs approximately 5-8 days after the transfusion.  Clinical presentation is similar in its severity to drug induced immune thrombocytopenia with levels dropping below 20,000 and sudden onset of bleeding. (Ref 1)
	DIC	Can occur in the setting of severe infection as mentioned above.  Can occur after significant surgeries presenting with an acute thrombocytopenia immediately after surgery with a bleeding diathesis that is more severe and more extensive than that which is expected from the degree of thrombocytopenia (because it is also associated with a coagulopathy).  DIC, not in the setting of infection, is hypothesized to be initiated by extensive surgical injury to the endothelium of the blood vessels and alteration of function of the endothelial cell. (Ref 1)
	TTP	Rare. Decreased platelets, increased LDH, normal PT/PTT. (Ref 1)

Other etiologies not specific to the postoperative setting should also always be considered including ITP, sequestration, malignancy-associated. 

• Labs:  Consider the following studies however send only those that are appropriate to the clinical situation:  CBC, reticulocyte, haptoglobin, coags, fibrinogen and peripheral smear
• Consultation:  Consider hematology consult especially when no obvious etiology and/or if levels low enough that you are considering platelet transfusion.

Treatment

• Platelet transfusions usually indicated only for platelets <10K and/or <50K and bleeding—important to discuss with the surgical team.
• Avoid intramuscular injections when thrombocytopenic (Ref 2)
• Avoid other drugs that interfere with platelet function (NSAIDs, ASA, beta-lactam antibiotics).

HEPARIN-INDUCED THROMBOCYTOPENIA (HIT)
HIT is an increasingly recognized cause of perioperative complications, including skin necrosis, DVT, pulmonary embolism, venous sinus thrombosis, and stroke.  In general, the benefits of heparin administration outweigh the risk of HIT, but it must be recognized in order to treat and prevent potentially catastrophic complications.

When to suspect

1. Unexplained thrombocytopenia 2. Thrombosis associated with thrombocytopenia 3. Platelet count that has fallen 50 percent or more from a prior value (note may still be in the normal range) 4. Necrotic skin lesions at heparin injection sites AND Prior exposure to heparin

• Platelet counts do not usually fall below 20,000 as a consequence of HIT, and other causes (drug-induced thrombocytopenia, DIC, ITP, etc.) should be suspected. 
• Non-immune-mediated decrease in platelet count is seen in many patients within 2 days of starting heparin, but causes a lesser drop and will usually rebound despite continued heparin treatment.
• Postoperative patients (particularly those with long spine surgeries) often have depressed platelet counts for days postoperatively, but if the platelet count fails to rebound or starts to fall, a diagnosis of HIT should be entertained.

Time Course
Varies depending on the patient's prior exposure to heparin (and whether they already have antibodies).  It is important to realize that a patient may present with HIT after stopping heparin.

Early	Within the first 1-2 days of starting heparin	Usually seen in patients with prior exposure to heparin, and hence prior antibodies
Usual	Within 4-10 days of starting heparin therapy	Presumed to be due to the formation of new antibodies.
Late	After discontinuation of heparin therapy.  May be > 2 weeks or more from last exposure to heparin.	Often after the patient's discharge from the hospital.  Suspect in a patient returning to the hospital with a new thrombotic complication, particularly after an orthopedic or other surgery where heparin prophylaxis was used.

Diagnosis
HIT is a clinical diagnosis, but certain lab tests are useful in supporting the diagnosis.  HIT is caused by antibodies against the heparin/platelet factor 4 complex, and multiple tests assess for the presence of these antibodies.  The ELISA immunoassay that is the most common test used is extremely sensitive but not specific, and hence a negative test can be useful in ruling out the diagnosis, but does not confirm it without further supporting features.  The UWMC anticoagulation clinic (uwmcacc.org) recommends first checking heparin antibody ELISA assay.  If positive and high clinical suspicion then treat as HIT positive.  If high clinical suspicion of false positive, can test heparin antibody SRA assay. (Ref 5)

Treatment

• Stop all heparin products (this includes heparin flushes)
• Start a non-heparinoid anticoagulant (direct thrombin inhibitors argatroban and lepirudin are approved for use in the US)—pharmacy protocols exist for this treatment and will vary from hospital to hospital
• Start warfarin (only AFTER non-heparinoid anticoagulant has been started) with a plan to anticoagulate for at least 6 weeks, but NOT until the patient's platelet count is greater than 100K due to the risk of transient hypercoagulability
• Therapy should be overlapped for at least 5 days prior to discontinuation of the direct thrombin inhibitor
• Hematology consult should usually be involved in treating hospitalized patients with HIT.

Prevention

• Low molecular weight heparins (enoxaparin, dalteparin, et al.) appear to have a lower risk of HIT, and should be used when appropriate
• Avoid unnecessary use of heparin

Can patients with a history of HIT ever be rechallenged with heparin?
While not recommended if other forms of anticoagulation are available, most patients with immune-mediated HIT lose their HIT antibodies within 3 months of ceasing therapy, and short-term heparin use (such as for cardiac bypass surgery) has been shown to be safe.4 Dialysis patients have also been retreated with heparin without incident, but this data is still forthcoming.

References

• 1. Uptodate.com. Approach to the Adult Patient with Thrombocytopenia. Topic last updated 3/23/2010.
• 2. Chang JC. Review: Postoperative thrombocytopenia: with etiologic, diagnostic and therapeutic consideration. Am J Med Sci. 1996 Feb;311(2):96-105.
• 3. Coutre, S. Heparin-induced thrombocytopenia.  http://www.uptodateonline.com .  Topic date 9/13/06.
• 4. Follis F, Schmidt CA.  Cardiopulmonary bypass in patients with heparin-induced thrombocytopenia and thrombosis.  Ann Thorac Surg.  2000;70:2173-2181.
• 5. http://uwmcacc.org/pdf/VTE_HIT.pdf

Updated May 2011