A 71-year-old patient with advanced chronic renal failure secondary to ischaemic nephroangiopathy and atrial fibrillation was treated for progressive asthenia and a glomerular filtration rate below 10ml/min.
It was not possible to perform arteriovenous fistula due to poor arterial and venous development in the upper limbs.
Three days before the first dialysis session, the administration of low molecular weight heparin is started instead of its usual anticoagulant.
A left jugular tunneled catheter was inserted, receiving usual doses of heparin to prevent clotting of the circuit and unscheduled heparin for catheter lock.
Platelet count is 210x109/l.
The first sessions are unsatisfactory due to low catheter performance.
Nine days after the first administration of heparin, in its fourth dialysis session, there was a first acute event: sudden dyspnea and precordial pain at the beginning of the session without hypotension, hemoptysis or fever.
pulmonary oedema, pulmonary oedema, pulmonary oedema, pulmonary oedema lon
No skin rash.
Hemoglobin: 9.6g/dl, leukocytes: 7200.
Platelets: 44x109/l, lactic dehydrogenase (LDH): 510U/l, cardiac troponin 1 (cTnI): 2.6ng/ml.
No signs of ischemia or injury on the electrocardiogram.
The patient remains under observation for 24 hours with clinical normalization (as during the course of the session) and a significant decrease in cTnI to 1.2ng/ml.
Radiology did not provide relevant data.
1.
Polyisolate sterilized with vapor was the filter used.
Hemodialysis was conventional with volume control.
He did not receive therapy with renin-angiotensin system blockers, but beta-blockers and calcium antagonists.
At this time, it was not noticed that on the factory information about the catheter there was sterilization with ethylene oxide and its impregnation with heparin.
Heparin was suspended when HIT II was suspected, following successive sessions with multiple problems of catheter flow and resistance, in addition to repeated coagulation of the circuit.
Pending treatment with argatroban, the tunneled jugular catheter is replaced by another catheter of similar characteristics, without improving performance, so a cervical computerized axial tomography is performed, reporting as partial thrombosis.
Two days later, the patient came asymptomatic to the unit, but 10 minutes after the connection he experienced a new episode of sudden dyspnea with p02 of 78%, which he recovered with usual support measures during hospitalization.
The platelet count is 101x109/l, lower than the previous days.
Forty-eight hours later platelets are 162x109/l.
Finally, argatroban is available, which is administered at the previously described dose of 2590mic/kg bolus at the beginning of the session and in subsequent infusion of 2mic/kg/min, ending 1 hour before the session.
Controls of : activated partial thromboplastin time (APTT) were maintained at recommended margins of 1.5 to 2.5 above baseline.
From there, clotting of the circuit disappeared and the performance of the same catheter was excellent.
While waiting for the start of treatment with the trombin inhibitor as well as after until the patient finally started peritoneal dialysis, clopidogrel treatment was prescribed.
It is explained by the threat of new punctures of central vessels and two pending surgical interventions: peritoneal catheter and transurethral resection of small bladder tumor, although the latter was already performed peritoneal dialysis.
At no time before transfer to the referral center for switching to the SUD, argatroban and coumarins were administered concomitantly.
It should be noted the absence of data on acute venous thrombosis and that heart rate was controlled.
1.
Clinical and laboratory data
HIT II is defined as a 50% drop in platelet counts below 100x109/l occurring within 5 to 15 days of the first exposure.
In our setting this entity has not gone unnoticed6-8.
The considerable risk obligates to act quickly.
The diagnosis is established by functional and antigenic tests.
The first ones, with higher specificity: STRA (14C serotonin release assay), according to their specificity (heparin induced platelet activation assay) and PAT (platelet aggregation test)9,10, have the main drawback of not being available.
Antigenic tests by ELISA and the PaGIA test (particle gel immunoassay) do not reach this percentage of specificity11.
Diagnosis
The clinical process admits other assumptions: the allergic reaction to ethylene oxide12 usually manifests with skin reaction and does not explain thrombocytopenia or rapid recovery without antihistamines.
No determination of ethylene oxide antibodies was performed.
Another entity with similar clinical presentation is the anaphylactic reaction when negative load filters are used in patients treated with blocking of the renin-angiotensin system by activating the recibía βquinina patient13,14, drugs
Other pollutants or sterilizers in the circuit seem very unlikely in haemodialysis with current control systems.
The programmed determination of endotoxins in the dialysing fluid was always normal.
In extracorporeal treatment, it is mandatory to rule out air embolism, hemolysis and acute anemia.
The visible area of the catheter was intact and no leaks were detected in the circuit.
There were no hemolysis data, with LDH determination of 501 U/l.
Situations inherent to the patient's pathology, such as pulmonary edema, acute myocardial infarction, embolism or pericardial tamponade, are discarded in the clinical, biological and radiological context.
It is true that there was some myocardial suffering due to the increase in cTnI levels, but without electrocardiographic repercussions.
As for the possibility of septic process, it seems unlikely without fever or leukocytes, so procalcitonin was not determined.
Thrombocytopenia is not explained by the usual pharmacology of the patient, nor by pulmonary sequestration with biocompatible filters, sepsis, disseminated intravascular coagulation (DIC), which is confirmed by the Hematology service.
Taking into account the chronopathology of the event and following the parameters of the mentioned test (table 1) with a subjective score of risks 7, we adjusted for a diagnosis of presumption of TIH II, supported later positive ELISA.
Table 2.
Diagnostic probability in heparin-induced thrombopenia on haemodialysis (three clinical factors and ELISA)7 ELISA: enzyme-linked immunoassay; SRA: serotonin.
1.
Treatment
Diagnostic confirmation by laboratory tests should not be expected when there is a strong clinical suspicion.
The first step is to remove heparin.
The drugs indicated are trombin inhibitors: lepidurine, bivalirudin and argatroban.
The former has the disadvantage of producing anaphylaxis and its elimination is renal.
Nowadays it is not available, although it has been used successfully in our environment.
The use of bivalirudin is widespread in the catheterization laboratory due to its short half-life, but also renal elimination.
Argatroban has no renal elimination and therefore appears more appropriate in Nephrology; it is acquired as a foreign drug.
Argatroban16 is a synthetic inhibitor of the thrombin, which binds selectively and reversibly.
It has a short half-life, so its effect disappears rapidly after suspension.
It is not immunogenic and does not require dose modification in renal impairment.
It is able to inhibit both free and clot-bound trombin.
It is metabolized in the liver and biliary excretion, and finally in faeces.
Steady-state concentrations are reached within 1-3 hours and the effect disappears within 1-2 hours after cessation of dosing.
Adverse Reactions
Studies in haemodialysis 18-20 and hemo21 demonstrated elimination of up to 20%, taking into account the non-existence of medication.
The often necessary transition from argatroban to coumarins should be careful because of the risk of necrosis, proteins and lower limb amputations caused by the effect of coumarins,23 S.
Thrombin inhibitors alter international normalized ratio (INR) values due to their high osmolar concentration.
It is accepted in practice that, once platelet counts are normal, argatroban and acenocoumarol are concomitantly administered for at least 4-5 days until INR>4.
Argatroban was then suspended and a new INR control was performed at 6 hours.
It has been shown that during the combined administration of both drugs with INR>4, the relationship between INR and bleeding is altered, with a higher risk of bleeding.
Even if a patient was on a dicumarinic anticoagulant and adhered to TIH II, vitamin K should be administered to reverse the increased risk in this context.
