​Kembara Xtra - Medicine - Heparin Induced Thrombocytopenia

​Kembara Xtra - Medicine - Heparin Induced Thrombocytopenia 
Platelet count falling by 50% or more from baseline is a potentially fatal side effect of heparin usage.
- A 5 to 10% daily risk of thromboembolism, death, and amputation

Antibody-mediated prothrombotic disease brought on by the use of heparin
Heparin-induced thrombocytopenia (HIT) is a unique reaction that causes thrombosis rather than bleeding, in contrast to other thrombocytopenias.
Heparin-induced thrombocytopenia/thrombosis (HITT) (immune-induced; formerly known as HIT type II) and nonimmune heparin-associated thrombocytopenia (formerly known as HIT type I).
Nonimmune heparin-associated thrombocytopenia (HIT) is more prevalent, appears 1–4 days after beginning heparin, has few consequences, and the platelet count may spontaneously return to normal.
- Immune HITT: less frequent, manifests 5 to 14 days after initial heparin exposure, thrombocytopenia frequently 100,000/mm3, but typically >20,000/mm3, and carries a high risk of fatal thrombosis.

HIT can present with one of three onset patterns: quick, typical, or delayed. HIT can present with one of three onset patterns: quick, typical, or delayed.
- In 60% of the instances, a typical pattern is visible, leading to a decrease in platelet reduction 5 to 10 days after exposure.
Delayed-onset pattern occurs on average 9.2 days after the start of heparin products. Rapid pattern is evident in 30% of instances with platelet count reduction occurring immediately after exposure to any heparin product. Even after stopping the use of heparin, it can arise.

Prevention Incidence

Regardless of dosage, timing, or route of delivery, thrombocytopenia will occur in 0.1–5% of heparin-treated individuals.

Of these patients, 25–50% will experience HITT.


Pathophysiology and Etiology 

Nonimmune heparin-associated thrombocytopenia may be brought on by heparin's direct platelet membrane binding.
HITT: Heparin can raise the level of the chemokine platelet factor 4 (PF4) in the circulation. Heparin, which serves as a substrate for immunoglobulin (IgG) antibodies, will combine with PF4 to create a complex. Heparin/PF4 complex can, in turn, encourage the formation of specific antiheparin/PF4 complex antibodies. IgG antibodies detect neoepitopes on PF4 and the resulting complex stimulates monocytes and platelets, increasing generation of thrombin and platelet-fibrin thrombi.
Platelet activation and a prothrombotic condition are brought on by these antibodies. In the end, many individuals experience thromboembolic problems as a result of this hypercoagulable state.

Heparin flushes, such as those used for arterial lines or heparin locks, are sources of the drug.
Unfractionated heparin (UFH) and catheters with heparin bonds
Enoxaparin and dalteparin are examples of low-molecular-weight heparin (LMWH).

Postsurgical, medical, and obstetric risk factors
The greatest risk factor is postcardiopulmonary bypass (CPB). The risk is higher for surgical or trauma patients than for medical or ICU patients.
Bovine UFH is 10 times more dangerous than LMWH; porcine UFH is superior to both.
Male > female
Heparin use for more than five days causes a higher decrease in platelet count than preventive anticoagulation does.
Rare in women who are pregnant


Prevention 

Ask about recent exposure to heparin and any prior history of HIT. Use of LMWH (instead of unfractionated), for a shorter period of time, can lower the chance of getting HIT.

 Clearly describe prior HIT reactions in the patient's medical file. Create a protocol for identifying and treating HIT. Once the condition has been identified, no heparin should be given.

Accompanying Conditions 
Venous thrombosis, including deep vein thrombosis (DVT), pulmonary embolism (PE), and adrenal vein thrombosis with hemorrhagic infarction, is more common in patients undergoing medical treatment and following orthopedic surgery.
Arterial thrombosis: observed more frequently in patients undergoing vascular and cardiac surgery; causes myocardial infarction, stroke, mesenteric infarction, and limb ischemia.
Acute systemic responses, skin lesions (including skin necrosis at the injection site), and


Nonimmune heparin-associated thrombocytopenia (HIT) is characterized by an asymptomatic decrease in platelet count. Heparin-dependent antibody thrombocytopenia (HITT) is characterized by thrombocytopenia or thrombosis. Both clinical and serologic results serve as the basis for diagnosis.

Providing a history that includes: the length of current heparin therapy; previous exposure to heparin, such as through heparin flushes and catheters coated with heparin;
Consider HITT as a potential cause in patients who are receiving heparin therapy for thrombosis and who experience recurrent thrombosis while receiving treatment.
Clinical rating scales:
– The "4 Ts" methodology, often known as risk stratification
 New-onset thrombocytopenia
 Thrombocytopenia's onset (5–10 days after exposure) New-onset thrombosis
Other causes of thrombocytopenia have been ruled out.
Low 4Ts score is connected to a high HIT negative predictive value.
High (>6) and Intermediate (4-5) exhibit HIT-predictive positive values. An efficient pretest probability technique is the HIT Expert Probability score.
– System of post-CPB scoring

clinical assessment 
Skin necrosis (which starts as erythema and proceeds to ecchymosis and necrosis) is one of the symptoms of venous or arterial thrombosis.
Ischemic alterations (symptoms of mesenteric, renal, splenic, and limb ischemia)
bleeding (less frequent)

 Acute systemic reactions following an IV bolus of heparin, such as anaphylaxis symptoms


Multiple Diagnoses 

The following additional (not exhaustive) reasons of thrombocytopenia may also occur.
Drug interactions, autoimmune responses, transfusion reactions, physical harm (such as during CPB), sepsis and other infections, drug reactions, autoimmunity


Laboratory Results 
Serial platelet counts in heparin-treated individuals with a potential risk of HITT >1% Assess platelets at the beginning of heparin therapy and subsequently every two to three days from days four to fourteen:
- Withhold platelet monitoring for heparin-treated patients who have an HITT risk of less than 1%.
The two main categories of confirmatory lab tests for a clinical diagnosis are:
- Antigen assay to find anti-PF4 antibodies present:
 ELISA has a strong negative predictive value for HIT but is only up to 99% sensitive.
- A functional assay to look for signs of platelet activation when heparin is present:
The gold standard for diagnosis, the serotonin release assay (SRA), has a high level of specificity and sensitivity.
High specificity and low sensitivity of heparin-induced platelet activation (HIPA)
The first test should be an antigenic assay. A functional assay or an antigenic assay by themselves would not be sufficient for clinical diagnosis; their combination is typically advised.
Because HIT is a clinicopathologic illness, the diagnostic interpretation of these laboratory tests must be done in the context of the clinical evaluation of the pretest probability. Even if patients develop heparin-dependent antibodies, HIT may not occur.

Management 

Heparin must be promptly stopped and replaced with an appropriate alternative anticoagulant as part of the treatment plan.
It is NOT recommended to use LMWH to treat HIT.

Prevention 

 Stop using any heparin-containing products, including flushes and catheters with heparin coating.
Due to their increased thrombotic risk, all patients with a diagnosis of HIT should undergo alternative anticoagulation.
When heparin is withdrawn, nonimmune heparin-associated thrombocytopenia usually goes away.

Caution 
Transfusions of platelets may lead to more thrombosis. Warfarin should not be delivered until platelet recovery. Platelet transfusions should only be given if bleeding or during an invasive procedure with a significant risk of bleeding.  Adverse reactions to heparin should be thoroughly documented in the patient's medical record with instructions to avoid all heparin products. If warfarin has been given, vitamin K should be given due to depletion of proteins S and C and increased risk for venous limb gangrene.
If the absence of heparin/PF4 complex antibodies can be verified, the administration of heparin for a brief period of time may be tolerated for individuals with a history of HIT under specific circumstances (such as the necessity for CPB). Postoperative thrombotic events are much more common in patients who acquire antibodies to the heparin/PF4 combination than in patients who do not.


Management 
The majority of patients need anticoagulation due to: - Preexisting thrombosis or - Risk of thrombosis in the first 30 days following HIT diagnosis (Take into account anticoagulation for 30 days.)
Anticoagulant dosage is determined by the indication (prophylaxis vs. treatment):
- In situations where a laboratory confirmation is forthcoming and there is a clinically low suspicion or pretest probability of HIT, it may be prudent to maintain antithrombotic prophylaxis using nonheparin anticoagulants.
- It is advisable to start anticoagulation treatment with a nonheparin product in situations when there is a strong suspicion or pretest probability of HITT.

Direct thrombin inhibitors (DTIs), such as argatroban and bivalirudin, reduce the relative risk of thrombosis by 30% but are linked to a 5–10% risk of bleeding.
– can cause a false-upward trend in the international normalized ratio (INR) (presumably due to an in vitro reaction).
For the treatment of HITT or in patients having percutaneous coronary intervention when heparin is contraindicated, argatroban is now approved.
Initial dose of 2 g/kg/min via continuous IV infusion; patients with acute illnesses or decreased hepatic function should receive a lower dose of 0.5 to 1.2 g/kg/min.
Activated partial thromboplastin time (aPTT) should be increased by 1.5 to 3 times the baseline by dose changes due to the very short half-life of the drug. Argatroban dose adjustment is necessary for individuals with hepatic dysfunction because the activated partial-thromboplastin time may be erroneously high when given to patients who have additional coagulopathies. Bivalirudin's dose is unaffected by renal function.
Reduced risk of bleeding in patients having percutaneous vascular interventions (PCIs) and other cardiac operations. Off-label use for HIT complicated by thrombosis.
 0.15 to 0.20 mg/kg/hr as the initial dose; 1.5 to 2.5 times the baseline aPTT adjustment.
Drug elimination varies depending on GFR. A patient with normal renal function has a half life of 25 to 30 minutes, while a patient with end-stage renal disease has a half life of 3.5 hours.
Inhibitors of factor Xa (2)[A]
Factor Xa therapy reports are thought to be helpful, but there is little evidence to confirm their effectiveness for HIT, and the appropriate dose has not yet been established.
– Fondaparinux has not been advised due to a lack of evidence; nevertheless, Rivaroxaban has been extensively examined and offers evidence for HIT management.

Warfarin transition: Must first use an immediate-acting anticoagulant before beginning warfarin; Start taking warfarin when platelet count is greater than 150,000/mm3; Stop taking other anticoagulants; only take warfarin when INR is therapeutic (between 2 and 3) for at least 5 days. This therapy is different from the typical switch from heparin to warfarin in other anticoagulation-required conditions.

LMWH - Although there is a decreased chance that LMWH will cause an HIT reaction, it shouldn't be used if there are already antibodies present since they will react with LMWH and cause thrombosis and thrombocytopenia.

Admission 

Avoid platelet transfusions and heparin flushes; HIT in pregnancy is uncommon. Although their safety has not been shown, therapeutic medicines may be useful in preventing thrombotic problems.

Follow-Up In individuals with HIT, the gap between starting anticoagulation with a DTI and warfarin might be challenging.
Before stopping the DTI, the INR should be therapeutic (2 to 3) when taking both warfarin and a DTI for at least five days.
It is best to wait to start warfarin therapy until the platelet count has stabilized within a normal range.At least three months should pass after the start of therapy.
DTIs can increase INR, thus if your INR is below 4 while taking warfarin plus a DTI, you should temporarily stop the DTI for 4 to 6 hours and check your INR again. This second INR will just reflect the anticoagulant effects of the warfarin.

Serial platelet counts, PTT monitoring, and INR monitoring, as measured by the anticoagulant, are all aspects of patient monitoring.


Prognosis: Thrombosis in HIT carries a death rate of 20–30% along with additional morbidities such stroke and limb ischemia.
Within weeks of quitting heparin, platelet levels return to normal.

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