This document discusses Heparin-Induced Thrombocytopenia (HIT). It covers the immunology of HIT including how antibodies form against platelet factor 4. It describes the clinical presentations of HIT focusing on the 4Ts criteria of thrombocytopenia, timing of platelet drop, thrombosis, and other causes. It discusses laboratory diagnosis using assays to detect antibodies. The document concludes with sections on treatment options including alternative anticoagulants and managing HIT in different clinical scenarios.
TEG - Thromboelastography
Thromboelastography is a viscoelastic hemostatic assay that measures the global visco-elastic properties of whole blood clot formation under low shear stress
it shows the interaction of platelets with the coagulation cascade (aggregation, clot strengthening, fibrin cross linking and fibrinolysis)
does not necessarily correlate with blood tests such as INR, APTT and platelet count (which are often poorer predictors of bleeding and thrombosis)
This includes scores, prehospital and emergency department management of stroke. it goes into details of stabilisation and general management. definitive management options are thrombolysis or thrombectomy. briefly described complications of stroke and management as well
Physiology of coagulation.
Coagulation disorders, evaluation, treatment and anaesthetic implications.
Thromboelastography and its relevance to Liver transplant and anaesthetic management of the same. Complete with TEG images of liver transplant patients at various phases of the surgery
Common Diagnostic pitfalls with coagulation disorders lies in addressing challenges in preanalytical processes & implementation of algorithms as per newer guidelines.
TEG - Thromboelastography
Thromboelastography is a viscoelastic hemostatic assay that measures the global visco-elastic properties of whole blood clot formation under low shear stress
it shows the interaction of platelets with the coagulation cascade (aggregation, clot strengthening, fibrin cross linking and fibrinolysis)
does not necessarily correlate with blood tests such as INR, APTT and platelet count (which are often poorer predictors of bleeding and thrombosis)
This includes scores, prehospital and emergency department management of stroke. it goes into details of stabilisation and general management. definitive management options are thrombolysis or thrombectomy. briefly described complications of stroke and management as well
Physiology of coagulation.
Coagulation disorders, evaluation, treatment and anaesthetic implications.
Thromboelastography and its relevance to Liver transplant and anaesthetic management of the same. Complete with TEG images of liver transplant patients at various phases of the surgery
Common Diagnostic pitfalls with coagulation disorders lies in addressing challenges in preanalytical processes & implementation of algorithms as per newer guidelines.
Management of Immunogenic Heparin-induced Thrombocytopeniaasclepiuspdfs
Immunogenic heparin-induced thrombocytopenia (HIT) is an immune response to heparin associated with significant morbidity and mortality in hospitalized patients if unidentified as soon as possible, due to thromboembolic complications involving both arterial and venous systems. Early diagnoses based on a comprehensive interpretation of clinical and laboratory information improve clinical outcomes. Management principles of strongly suspected HIT should not be delayed for laboratory result confirmation. Treatment strategies have been introduced including new, safe, and effective agents. This review summarizes the clinical therapeutic options for HIT addressing the use of parenteral direct thrombin inhibitors and indirect factor Xa inhibitors as well as the potential non-Vitamin K antagonist oral anticoagulants.
The Gram stain is a fundamental technique in microbiology used to classify bacteria based on their cell wall structure. It provides a quick and simple method to distinguish between Gram-positive and Gram-negative bacteria, which have different susceptibilities to antibiotics
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
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Knee anatomy and clinical tests 2024.pdfvimalpl1234
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CDSCO and Phamacovigilance {Regulatory body in India}NEHA GUPTA
The Central Drugs Standard Control Organization (CDSCO) is India's national regulatory body for pharmaceuticals and medical devices. Operating under the Directorate General of Health Services, Ministry of Health & Family Welfare, Government of India, the CDSCO is responsible for approving new drugs, conducting clinical trials, setting standards for drugs, controlling the quality of imported drugs, and coordinating the activities of State Drug Control Organizations by providing expert advice.
Pharmacovigilance, on the other hand, is the science and activities related to the detection, assessment, understanding, and prevention of adverse effects or any other drug-related problems. The primary aim of pharmacovigilance is to ensure the safety and efficacy of medicines, thereby protecting public health.
In India, pharmacovigilance activities are monitored by the Pharmacovigilance Programme of India (PvPI), which works closely with CDSCO to collect, analyze, and act upon data regarding adverse drug reactions (ADRs). Together, they play a critical role in ensuring that the benefits of drugs outweigh their risks, maintaining high standards of patient safety, and promoting the rational use of medicines.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
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This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
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Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
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New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
2. Overview
The Immunology of HIT
Clinical Presentations
Laboratory Diagnosis
Timing and degree of thrombocytopenia
Presence of thrombosis and implications for management
Rarer presentations
Heparin/PF-4 antibodies
Serotonin release assay, HIPA
Therapeutic Management
DTIs, fondaparinux
Vitamin K antagonism
With or without thrombosis
Cardiovascular surgery
Heparin re-challenge
Spontaneous HIT, Fondaparinux-induced thrombocytopenia, and others
ACP Guidelines 8th Edition, 2008
Warkentin recent reviews
ASH Educational Session
Paradigms and Paradoxes, J Thromb Haemost 2011; 9 (Suppl 1):105-117
3. HIT: Features
An atypical, drug-induced immune response with platelet-
activating IgG antibodies against a novel epitope of PF4
induced by stoichiometric amounts of heparin
A hypercoaguable state with a high risk of thrombosis,
amputation, and death due to activation of platelets,
endothelium, and WBC
A disease requiring a clinicopathologic diagnosis
4. HIT Immunology
PF4 and chondroitin sulfate released from activated platelets
PF4 forms dimers and tetramers—tetramers bind to surface of
platelets and to endothelial cells via GAGs
The presence of long chains of heparin allow for ultra-large
aggregates of PF4 tetramers to form
These ultra-large PF4 tetramers allows for the binding of IgG abs
which in turn bind to FcRγIIA receptors on platelets and
endothelium, leading to activation
5.
6. The Immunology of HIT
2days
2days
Unpredictable
•The HIT ab is detectable a full 4 days before the platelet count cross the 50% reduction line
•Therefore re-testing is unnecessary, although this doesn’t rule out human error
Warkentin et al. Blood 2009
7. Immunoglobulin Subtypes
•IgG elevation occurred later in the non-HIT group
•No significant differences in IgA or IgM levels between HIT and non-HIT patients
Warkentin et al. Blood 2009
8. Immunology of HIT
•PF4/Hep abs increase quickly like a
secondary immune response
•Unlike a true secondary immune
response, the antibodies are
relatively short-lived
• Cleared within 40-100days
•There is also no anamnestic
response
9. The Immunology of HIT: Summary
Difference in levels of antibody formation between HIT and non-HIT
was due to IgG levels
OD values are approximately 80% of maximal at the start of platelet
fall (before clinical susupicion), and higher at the time of 50%
reduction
Very rapid antibody response: median 4 days from heparin
administration
No typical Ig class switch response (e.g. IgM ->IgG)
No association between previous heparin exposure and timing of
antibody development
No anamnestic response in HIT; rapid reactions are from circulating antibody
Relatively rapid loss of antibody titers.
Warkentin et al. Blood 2009
12. The Four T’s
LOW: 0-3 points
INTERMEDIATE: 4-5 points
HIGH: 6-8 points
Lo et al., JThrombHaemost 2006
13.
14. The First T: Thrombocytopenia
Initial studies used an absolute platelet count
cut-off
Improved sensitivity with preserved specificity for
using a relative 50% drop (some suggest even
30%--the Brittish)
Platelet count may be normal even when
dropping; consider especially thrombocytosis
The relative drop is based on the platelet count
at initiation of heparin; especially important in
the post-surgical patient (the double dip)
The thrombocytopenia of HIT also tends to be
more mild than that seen with other drug
reactions
15. The Second T: Timing
For most patients, the drop will begin 5-10d after
the initiation of heparin (nadir 10-14d)
Upwards of 20% of patients will have drops after
heparin is stopped (delayed-onset HIT)
Some will have thrombosis prior to platelet drop
Early drops occur in patients with recent
exposure to heparin
Generally within 30-100days prior
Due to remaining PF4/heparin abs, NOT an
anamnestic response
16. The oTher T’s: Thrombosis and
oTher causes
More on these later
17. The 4 T’s: Clinical Score
Experts
Everyone Else
Experts
Lo et al., JThrombHaemost 2006
18. The 4 T’s: Correlation with Labs
Experts
Everyone Else
Lo et al., JThrombHaemost 2006
21. 4 T’s: Summary
A low clinical score reliably rules out HIT
No need for lab testing
No need to stop heparin
A high score has a poor positive
predictive value (in the wrong hands…)
May depend on the population
Doesn’t reflect two main clinical parameters:
patient population and type of heparin
Needs to be strictly applied
22. Rarer presentations of HIT
Anaphylactic reactions to
heparin infusion
N.b. anaphylactoid reactions
to OSCS in 2008
Necrotizing skin lesions at
injection sites
Platelets in the normal range
Especially, pts with ET and
other MPDs
Continued thrombosis despite
heparin
23. Over-diagnosis of a problem worth
worrying about
“Within the past 10-20 years, recognition of HIT has evolved from
gross underdiagnosis to wild overdiagnosis”
“In essence, the widespread detection of anti-PF4/heparin
antidoies by commerically-available PF-4 dependent
immunoassays has prompted an over-diagnosis of HIT”
However, given the clinical importance of diagnosis true HIT (as
relatively rare as it is), it is imperative to always consider it and
reassure oneself that it is not occurring.
26. Laboratory Methods:
Ig Detection Assays
•Confirm assay can also be performed with addition of excess heparin
Excess heparin should inhibit antibody binding and reduce OD
29. •Clinically irrelevant antibodies detected by EIAs (IgGAM>>>IgG)
•Note even SRA% is greater than clinical HIT positivity
•This is why HIT is a clinicopathologic diagnosis, and not a pathologic diagnosis alone
•>50% of CT surgery patients will have ab positivity even though 1% will have HIT
32. How to Treat HIT
Heparin: Stop it.
Alternative Anticoagulation: Start it.
Warfarin: Reverse it, delay it, and overlap it.
33. (Isolated)HIT and HITT
The difference is based on the presence of overt
thrombosis
With i-HIT, 4 limb dopplers should be performed
on all patients (50% silent VTE found)
Isolated HIT requires at least cessation of heparin
plus alternative anticoagulation until platelet
recovery; warfarin use and duration is uncertain
34. Risk of Thrombosis in Isolated HIT
•High risk of thrombosis mandates treatment with non-heparin
anticoagulant, likely beyond prophylactic dosing
AACP Guidelines, Chest 2008
35. Argatroban
2mcg/kg/min
For Bilirubin >1.5, 0.5mcg/kg/min
Likely for all severe illness
PTT based assay—will be confounded by
elevations associated with DIC seen in HIT as well
as by re-warfarinization
No studies outside of HIT
36. Lepirudin
Renally cleared
High incidence of antibodies after treatment; re-
treatment is not recommended
Maybe more effective than argatroban?
Limb loss: 5% with lepirudin, 13% with argatroban
Likely not more bleeding than argatroban
Dosing is a major issue, and should be based on
manufacturer and not trials:
Infusion rate of 0.1mg/kg/h
No bolus unless life or limb-threat: 0.2mg/kg
Same PTT goals
37. Bivalrudin
Only approved for use with PCI and cardiac
surgery
Lower antigenicity and less dependence on
renal clearnece than lepirudin
less effects on INR than argatroban
Only reports about use outside of PCI and CT
surgery in HIT; other studies outside of HIT
38. Fondaparinux
Some concern about cross-reactivity, but rare
Renally cleared
Long half life
No monitoring required, but anti-Xa can be used
and will not be confounded like PTT
Warkentin loves it
39.
40. Cardiac Surgery and PCI
Cardiac surgery options:
Re-challenge with heparin (esp >100d since HIT,
negative SRA); use only during procedure
Use Bivalrudin
Use Heparin + Tirofiban or Epoprostenol
Use Lepirudin
Use Argatroban
PCI options:
Argatroban
Bivalrudin
Lepirudin
(Note: no heparin re-challenge; may need later for
surgery)
41. Warfarin
Not to be restarted until platelets >150 or
‘significantly improved’
Argatroban and Lepirudin will affect INR
Fondaparinux and Bivalrudin will not
May be possible to use DTI and then change to
fondaparinux when platelets have recovered in
preparation for warfarin
42. Platelet Transfusions
Not absolutely contraindicated
Some concern regarding safety and
precipitation of thrombosis
May be more of an association than causal
Have a higher threshold to transfuse patients
with confirmed HIT, but give as needed for
significant bleeding and/or risk of bleeding
Usually platelets >30 with HIT and no bleeding
attributable to HIT
Co-existing conditions (DIC etc) may lower platelet
count more
44. Low Clinical Likelihood of HIT,
No Active Thrombosis
Do not send EIA or SRA and continue heparin
OR
If EIA/SRA sent-> switch to prophylactic dosing of
alternative (esp fondaparinux) and wait for
results (CYA)
45. Int/High Possibility of HIT,
Active Thrombosis
Send appropriate tests (EIA, SRA)
Reverse any warfarin with IV or PO vitamin K
Change to alternative anticoagulation based on
clinical setting
Wait for platelet recovery and then begin
warfarin with overlap if HIT confirmed
46. Low Likelihood of HIT with Thrombosis or
Int/High without Thrombosis
More difficult clinical situations
Trust the 4Ts– if truly low likelihood, continue
heparin
If Int/High and no renal failure or bleeding, single
dose of treatment dose fondaparinux until EIA
results may be good intermediate
47. Isolated HIT
Perform LE dopplers to assess for silent thrombosis
Begin alternative anticoagulation based on
clinical setting
?Begin warfarin when platelets recover and
continue for…
48. A History of HIT
First, confirm the history is true (retrospective 4T
analysis, review ELISA and look for prior SRA)
Check ELISA
If negative can rechallenge
If positive, check SRA
Can re-use heparin in situations such as
cariopulmonary bypass for brief periods
Use alternative anticoagulation in all other
settings, including pre- and post-operative
Editor's Notes
-Not so easy to apply accurately: the criteria are stringent
Evaluated in two clinical settings:Experts—authors at a single tertiary care centerEveryone Else: Anyone ordering an ELISA, mandatory part of test orderingNote:Distribution of patients is differentResults of the scores are different