Letter from the Editor

Your patient has low platelets. Think about bleeding before and after cath.

Morton Kern, MD Clinical Editor Clinical Professor of Medicine Associate Chief Cardiology University of California Irvine Orange, California mortonkern005@hotmail.com
Morton Kern, MD Clinical Editor Clinical Professor of Medicine Associate Chief Cardiology University of California Irvine Orange, California mortonkern005@hotmail.com
Hemoglobin is 10.6mg/dl; White blood cell count (WBC) is 11,000 cell/mm3; K+ (potassium) is 3.4meq/dl, platelet count of 65,000; Blood urea nitrogen (BUN) is 28mg/dl; Creatinine is 1.4mg/dl; International Normalized Ratio (INR) is 1.5. Should this patient continue in the lab or should you consult the physician and stop the procedure? In view of the unknown risks that these blood values portend, this patient’s procedure should wait until the physician has a clear understanding of the problems and the potential risk/benefits of performing angiography/percutaneous coronary intervention (PCI). The blood values indicate considerable caution must be used to avoid complications related to bleeding (INR, low platelets, anemia), arrhythmia (low K+), renal failure (elevated BUN/creatinine), infection (high WBCs). While most of these values are marginally abnormal (by this scenario’s intent), they should not be ignored. For this discussion, let’s focus on the low platelets and the potential for bleeding. What is a safe platelet count to perform arterial puncture? A platelet count of less than 50,000 should raise concern about significant bleeding after any puncture, arterial or venous. Platelet counts of less than 20,000 could be considered as an absolute contraindication for punctures. In some patients, especially those with renal failure, even platelet counts around 100,000 might be associated with some bleeding due to renal failure-related platelet dysfunction. We should understand the cause of low platelets before any invasive procedure. Although we may get through the cath without problems, the post-cath care may be complicated by significant bleeding, especially at the arterial puncture site. We should also be concerned about bleeding if an intervention, pacemaker insertion, intra-aortic balloon pump (IABP), or significant intracardiac catheter manipulations which might bruise or even puncture heart structures have been performed. Some maneuvers (e.g., a transseptal approach) are obviously associated with a high risk for bleeding even when coagulation functions are normal. For our patient above, in general we do not give platelets unless there is evidence of clinical bleeding or an emergency invasive procedure is required. If the procedure is urgent, the patient might then get a platelet transfusion before the procedure and if there were signs of bleeding, another afterward. What about a new low platelet count after cath? Is it HIT? In the setting of cardiac catheterization, low platelet counts post-procedure are most commonly related to drugs or exacerbations of pre-existing clinical conditions. Exposure to certain drugs leading to destruction of circulating platelets is often associated with potential for bleeding or (counter-intuitively, thrombosis in heparin immune thrombocytopenia, also known as HITT). Heparin-induced thrombocytopenia (HIT) is the most common drug-related cause of a drop in the platelet count. HIT has 2 presentations (Table 1). Type II HIT is different than other thrombocytopenias because it has an association with thrombosis, rather than only bleeding. To complicate matters, heparin is often given with other drugs, which may also cause drug-induced thrombocytopenia, such as platelet receptor inhibitors or antibiotics (Table 2). There are four major drug-related mechanisms which cause low platelets: 1) Quinine-type drugs induce antibodies that bind to membranes and protein. This is a rare occurrence, about 26 cases for 1,000,000 in patients receiving quinine, sulfonamides or non-steroidal anti-inflammatory agents. 2) Platelet receptor antagonists have a fibran-type drug reaction against the glycoprotein IIb/IIIa receptor which induces an antibody reaction. The incidence of this response is also rare, 0.2-0.5%. 3) Abciximab (ReoPro)-specific antibody against the chimeric Fab fragment of abciximab occurs in 0.5-1.0% after first exposure and 10-14% after second exposure to abciximab. 4) Unfractionated heparin binds to platelet factor 4, producing an immune complex. The specific antibody activates platelets through the Fc receptors. This response occurs in 3-6% of patients treated for at least seven days with unfractionated heparin. It is a rare occurrence with low-molecular-weight heparin.1 HIT can be a life-threatening disorder. Platelet counts are decreased 50% or more from baseline or less than 150,000/mm3, falling to as low as 30 to 40%. In contrast to most other thrombocytopenias, thrombotic complications develop in approximately 20-50% of these patients. The time of onset of thrombocytopenia after heparin administration varies according to the type of exposure. A delay of 5-10 days is usual in patients who have had no prior exposure, whereas a precipitous decrease in platelet count within 6-12 hours can occur in those who have detectable levels of circulating platelet antibodies. Platelet counts rarely fall below 10,000/mm3 and are rarely associated with bleeding. A typical recovery pattern within 4-14 days occurs after heparin discontinuation. Despite having a normal platelet count, the risk of thrombosis is more than 30 times that of the controlled population and remains elevated for days to weeks after discontinuation of heparin. With regard to the thrombotic complications, venous thrombosis predominates in medical and orthopedic procedures, whereas arterial and venous thrombosis occur with frequency in those undergoing cardiac or vascular surgery. When HIT is suspected, lab testing for heparin-dependent antibodies via serologic or functional assays can be performed to detect circulating IgG, IgA and IgM antibodies or measure platelet activation. The HIT Enzyme-Linked ImmunoSorbent Assay (ELISA) kits are easier to perform than functional assays and are the preferred test for the acute setting. The management of HIT involves cessation of all sources of heparin, including the heparin solutions used to maintain patency of access lines. Patients who have HIT should not be treated with low-molecular-weight heparin since there is a small but certain degree of cross-reactivity with the platelet factor IV. Warfarin is contraindicated in this condition, based on reports of warfarin-induced skin necrosis and gangrene of the limbs. Aspirin and the placement of the inferior vena cava filters are not considered adequate therapy. In patients requiring anticoagulation, direct thrombin inhibitors or heparinoids, including lepirudin, argatroban or bivalirudin, which directly inactivate thrombin, may be used. These agents have a short half-life and show no cross-reactivity to heparin. Additional therapies include danaparoid, a mixture of heparan sulphate and dermatan sulphate which catalyzes thrombin-mediated inhibition of factor X. This drug is not available in United States, but has been used elsewhere in the world. Documentation of HIT should be included in the patient’s record. Patients with HIT are commonly in need of additional coronary interventions and thus the staff must consider how best to manage these individuals on their return trip to the cardiac cath lab. What is the bleeding risk with an INR of 1.5? In general, we wait until the INR is ≤1.5 before proceeding with cath. The risk of bleeding is elevated for an INR above this level. If the patient is not on warfarin, then the elevated INR is either a lab error or likely related to some degree of liver dysfunction, hepatic congestion or early liver failure. Careful consideration to cath and intervention in these patients is warranted. If an urgent procedure is required, intramuscular vitamin K and or fresh frozen plasma (FFP) can be given. The reestablishment of therapeutic anticoagulation after the procedure may be delayed if vitamin K is given, but this is a trade-off between risk and benefit for this specific problem. In patients with a risk of bleeding, consideration should also be given to the hemoglobin. In our patient, a hemoglobin, or Hgb, of 10.6 would not necessarily raise undue concern, given this is a stable and chronic level. However, a low hemoglobin also reflects other conditions, such as anemia of chronic disease, renal failure, low-grade gastro-intenstinal bleeding or hematological malignancy. For most patients, cath can be performed safely with hemoglobin above 10mg/dl, but exceptions are made for urgent procedures, especially in those patients with chronic renal failure, who commonly have hemoglobin less than 8mg/dl. Cardiac cath in a patient with hemoglobin below 8mg/dl should be postponed, unless the procedure is an emergency. With any increased bleeding risk, a margin of safety with a near-normal hemoglobin is desirable. What about the hypokalemia, high BUN and creatinine, and elevated WBCs? All these issues can be considered as problematic in our index patient, but here the values are borderline abnormal and alone would not be indications to postpone cath. For this patient, the first decision is how critical is it to do the cath? The next consideration is what are the causes of the lab abnormalities? And finally, how well will the patient tolerate a procedure which may stimulate arrhythmias, challenge renal function and with a possible metal implant (stent) in the setting of underlying high WBCs with a question of hidden infection? Managing this patient’s course through the cath lab is part of the art of cardiac catheterization, which we will discuss in future editor’s corners. In summary, for the patient with low platelets, here are several suggestions: 1) Recheck the labs (pseudothrombocytopenia may occur if blood is collected in EDTA tubes, redraw in citrate tubes); 2) Understand the reason for low platelets; 3) Weigh the risk/benefits of the invasive approach needed for diagnosis (e.g., maybe computed tomography angiography [CTA] might answer the coronary artery disease question). 4) Transfuse platelets only if platelet count very low and procedure must proceed; 5) Watch for post-procedure HIT/ HITT and treat accordingly. Make friends with your hematologist. We will need his advice.
References
1. Arepally GM, Ortel TL. Clinical Practice. Heparin-induced thrombocytopenia. N Engl J Med 2006;355(8):809-817.