This document discusses various anticoagulant agents including heparin, low molecular weight heparins, synthetic heparin derivatives like fondaparinux and idraparinux, direct thrombin inhibitors like lepirudin and bivalirudin, and synthetic thrombin inhibitor argatroban. It provides details on their mechanisms of action, pharmacokinetics, therapeutic ranges, and comparisons between unfractionated heparin and low molecular weight heparins. Protamine sulfate is discussed as an antagonist for reversing heparin overdose.
heparin in detail : mechanism of action, pharmacokinetics, clinical uses, adverse effect and contraindication of heparin and low molecular heparin.
for undergraduates.
I am professionally pharmacist. These slides for clinical subject especially for pharmacy department students. I hope these students get more benefits about it.
(May 29th, 2024) Advancements in Intravital Microscopy- Insights for Preclini...Scintica Instrumentation
Intravital microscopy (IVM) is a powerful tool utilized to study cellular behavior over time and space in vivo. Much of our understanding of cell biology has been accomplished using various in vitro and ex vivo methods; however, these studies do not necessarily reflect the natural dynamics of biological processes. Unlike traditional cell culture or fixed tissue imaging, IVM allows for the ultra-fast high-resolution imaging of cellular processes over time and space and were studied in its natural environment. Real-time visualization of biological processes in the context of an intact organism helps maintain physiological relevance and provide insights into the progression of disease, response to treatments or developmental processes.
In this webinar we give an overview of advanced applications of the IVM system in preclinical research. IVIM technology is a provider of all-in-one intravital microscopy systems and solutions optimized for in vivo imaging of live animal models at sub-micron resolution. The system’s unique features and user-friendly software enables researchers to probe fast dynamic biological processes such as immune cell tracking, cell-cell interaction as well as vascularization and tumor metastasis with exceptional detail. This webinar will also give an overview of IVM being utilized in drug development, offering a view into the intricate interaction between drugs/nanoparticles and tissues in vivo and allows for the evaluation of therapeutic intervention in a variety of tissues and organs. This interdisciplinary collaboration continues to drive the advancements of novel therapeutic strategies.
Nutraceutical market, scope and growth: Herbal drug technologyLokesh Patil
As consumer awareness of health and wellness rises, the nutraceutical market—which includes goods like functional meals, drinks, and dietary supplements that provide health advantages beyond basic nutrition—is growing significantly. As healthcare expenses rise, the population ages, and people want natural and preventative health solutions more and more, this industry is increasing quickly. Further driving market expansion are product formulation innovations and the use of cutting-edge technology for customized nutrition. With its worldwide reach, the nutraceutical industry is expected to keep growing and provide significant chances for research and investment in a number of categories, including vitamins, minerals, probiotics, and herbal supplements.
DERIVATION OF MODIFIED BERNOULLI EQUATION WITH VISCOUS EFFECTS AND TERMINAL V...Wasswaderrick3
In this book, we use conservation of energy techniques on a fluid element to derive the Modified Bernoulli equation of flow with viscous or friction effects. We derive the general equation of flow/ velocity and then from this we derive the Pouiselle flow equation, the transition flow equation and the turbulent flow equation. In the situations where there are no viscous effects , the equation reduces to the Bernoulli equation. From experimental results, we are able to include other terms in the Bernoulli equation. We also look at cases where pressure gradients exist. We use the Modified Bernoulli equation to derive equations of flow rate for pipes of different cross sectional areas connected together. We also extend our techniques of energy conservation to a sphere falling in a viscous medium under the effect of gravity. We demonstrate Stokes equation of terminal velocity and turbulent flow equation. We look at a way of calculating the time taken for a body to fall in a viscous medium. We also look at the general equation of terminal velocity.
Seminar of U.V. Spectroscopy by SAMIR PANDASAMIR PANDA
Spectroscopy is a branch of science dealing the study of interaction of electromagnetic radiation with matter.
Ultraviolet-visible spectroscopy refers to absorption spectroscopy or reflect spectroscopy in the UV-VIS spectral region.
Ultraviolet-visible spectroscopy is an analytical method that can measure the amount of light received by the analyte.
Deep Behavioral Phenotyping in Systems Neuroscience for Functional Atlasing a...Ana Luísa Pinho
Functional Magnetic Resonance Imaging (fMRI) provides means to characterize brain activations in response to behavior. However, cognitive neuroscience has been limited to group-level effects referring to the performance of specific tasks. To obtain the functional profile of elementary cognitive mechanisms, the combination of brain responses to many tasks is required. Yet, to date, both structural atlases and parcellation-based activations do not fully account for cognitive function and still present several limitations. Further, they do not adapt overall to individual characteristics. In this talk, I will give an account of deep-behavioral phenotyping strategies, namely data-driven methods in large task-fMRI datasets, to optimize functional brain-data collection and improve inference of effects-of-interest related to mental processes. Key to this approach is the employment of fast multi-functional paradigms rich on features that can be well parametrized and, consequently, facilitate the creation of psycho-physiological constructs to be modelled with imaging data. Particular emphasis will be given to music stimuli when studying high-order cognitive mechanisms, due to their ecological nature and quality to enable complex behavior compounded by discrete entities. I will also discuss how deep-behavioral phenotyping and individualized models applied to neuroimaging data can better account for the subject-specific organization of domain-general cognitive systems in the human brain. Finally, the accumulation of functional brain signatures brings the possibility to clarify relationships among tasks and create a univocal link between brain systems and mental functions through: (1) the development of ontologies proposing an organization of cognitive processes; and (2) brain-network taxonomies describing functional specialization. To this end, tools to improve commensurability in cognitive science are necessary, such as public repositories, ontology-based platforms and automated meta-analysis tools. I will thus discuss some brain-atlasing resources currently under development, and their applicability in cognitive as well as clinical neuroscience.
The ability to recreate computational results with minimal effort and actionable metrics provides a solid foundation for scientific research and software development. When people can replicate an analysis at the touch of a button using open-source software, open data, and methods to assess and compare proposals, it significantly eases verification of results, engagement with a diverse range of contributors, and progress. However, we have yet to fully achieve this; there are still many sociotechnical frictions.
Inspired by David Donoho's vision, this talk aims to revisit the three crucial pillars of frictionless reproducibility (data sharing, code sharing, and competitive challenges) with the perspective of deep software variability.
Our observation is that multiple layers — hardware, operating systems, third-party libraries, software versions, input data, compile-time options, and parameters — are subject to variability that exacerbates frictions but is also essential for achieving robust, generalizable results and fostering innovation. I will first review the literature, providing evidence of how the complex variability interactions across these layers affect qualitative and quantitative software properties, thereby complicating the reproduction and replication of scientific studies in various fields.
I will then present some software engineering and AI techniques that can support the strategic exploration of variability spaces. These include the use of abstractions and models (e.g., feature models), sampling strategies (e.g., uniform, random), cost-effective measurements (e.g., incremental build of software configurations), and dimensionality reduction methods (e.g., transfer learning, feature selection, software debloating).
I will finally argue that deep variability is both the problem and solution of frictionless reproducibility, calling the software science community to develop new methods and tools to manage variability and foster reproducibility in software systems.
Exposé invité Journées Nationales du GDR GPL 2024
Salas, V. (2024) "John of St. Thomas (Poinsot) on the Science of Sacred Theol...Studia Poinsotiana
I Introduction
II Subalternation and Theology
III Theology and Dogmatic Declarations
IV The Mixed Principles of Theology
V Virtual Revelation: The Unity of Theology
VI Theology as a Natural Science
VII Theology’s Certitude
VIII Conclusion
Notes
Bibliography
All the contents are fully attributable to the author, Doctor Victor Salas. Should you wish to get this text republished, get in touch with the author or the editorial committee of the Studia Poinsotiana. Insofar as possible, we will be happy to broker your contact.
7. • Heparin so named as it was first extracted from liver.
• It is a mixture of sulfated mucopolysaccharides with a molecular weight
ranging from 10000-40000.
• It is a strong electronegatively charged acidic polymer.
• It is present together with histamines in all tissues containing mast cells
but richest source are lungs, liver and intestinal mucosa.
• Commercial preparations are obtained from beef lung, and pig intestinal
mucosa and standardized after biological assay.
9. • Antithrombin III plays a crucial role in natural endogenous anticoagulant
mechanisms in the body by blocking the activity of activated clotting
factors 12, 11, 10, 9 and 2 (thrombin)
• Under physiological settings, these interactions are slow and work on
demand and supply basis.
• But heparin accelerates ATIII activity by 1000 folds especially against IIa
and Xa.
10. • However factors like 9, 11 and 12 are also affected.
• Both thrombin IIa and factor Xa are sensitive to the inhibitory effects of
high molecular weight heparin ATIII complex.
• But IIa inhibition is much more than Xa.
• After binding heparin induces a conformational change in ATIII to expose
and makes it reactive site more accessible for IIa/Xa binding.
11. • Once the heparin ATIII clotting factor ternary complex is formed, heparin is
released for renewed interaction with another ATIII molecule.
• On the contrary only factor Xa is sensitive to the inhibitory effects of low
molecular weight heparin-ATIII complex, thrombin is not.
• Reason: LMWH is too a small molecule compared to heparin to bind AT III
as well as thrombin simultaneously.
• Heparin in higher doses also inhibits platelet aggregation but this action is
secondary to its inhibitory effects on thrombin, which itself a powerful
platelet aggregating agent.
15. • Being a large and highly ionized molecule, heparin is not absorbed from
GIT.
• It doesn’t cross BBB or placental barrier.
• Its ca2+ or Na+ salts are given by constant IV injection or by deep
S.C.injection.
• It is not administered IM to avoid hematoma formation at injection site.
• Low dose s.c. injection is usually preferred for prophylaxis(1-2hrs before
operation and continued till patient is discharged)
16. • However bioavailability by this route is inconsistent and anticoagulant
effects appear after an hour.
• It is metabolized in liver by heparinase.
• It exhibits dose dependent metabolism.
• The half life increases with increasing dose.
• The duration of action of heparin being short(1-5 hrs), its dose is adjusted
that the whole blood clotting time is raised to 2-3 times more than
normal Or APTT is raised to one and half –two times of normal values.
25. • Psuedo resistance causes
Because of higher
concentrations of factor
8 and fibrinogen
26. • True heparin resistance causes
High plasma level of
proteins that compete
with antithrombin for
heparin binding
Antithrombin deficiency
27. • Dose adjustments
not needed in
pseudoresistance
Because antifactor Xa
level is therapeutic
In true resistance
heparin dose needs to
be increased
Until therapeutic aPTT
or anti-factor Xa level is
achieved.
28. • Patient with anti-
thrombin deficiency
Requires antithrombin concentrate to achieve
therapeutic anticoagulation with heparin
29. Heparin dose adjustments
• PTT<35 – 80 units/Kg bolus units. Increase drip 4 units/kg/hr.
• PTT 35 to 45 – 40 units/Kg bolus units. Increase drip 2 units/kg/hr.
• PTT – 46-70 – no change
• PTT 71-90 – reduce drip 2 units/kg/hr
• PTT> 90 – hold heparin for 1 hr and then reduce drip 3 units/kg/hr
• Order a PTT 6hrs after any dose change, adjusting heparin infusion by the
sliding scale until PTT is therapeutic (46-70 seconds).
• When 2 consecutive PTTs are therapeutic, order PTT and readjust heparin
drip as needed every 24 hrs.
31. • Enoxaparin, dalteparin, ardeparin, nadroaparin, parnaparin, reviparin and
tinzaparin.
• UFH unfractioned heparin has a molecular weight ranging from 5000-
30000.
• On fractionation, it provides high MW heparin and Low MW ranging from
2000-9000 heparins.
• The latter have a short polymer length and inhibit activated factor X
predominantly but have lesser effect on thrombin, platelet function and
on coagulation in general.
• Thrombocytopenia is less frequent and chances of hemorrhage are less.
32. The more important avantages of
LMWH are their pharmacokinetic
features:
• These can be given S.C.
• Because of better bioavailability 70-90% by S.C route variability in
response is minimized.
• They have a longer elimination half life and are eliminated by first order
kinetics so the effects are more consistent.
• Dose is given in mg not in units can be easily and calculated on body
weight basis.
33. • And dosing less frequent once daily S.C.
• These donot prolong aPTT and whole blood clotting time. Hence response
is predictable and monitoring is not required as routine as UFH.
35. • The need to use a heparin antagonist is rare because the duration of
action of heparin being short.
• The discontinuation of heparin in most cases solves the problem.
• Even otherwise blood transfusion is necessary if bleeding occurs to
compensate the loss.
• However in certain conditions e.g. in cardiac surgery and vascular surgery,
there comes a need to terminate heparin action rapidly.
• Protamine sulfate is a specific antagonist for heparin overdose.
36. • It is a strongly basic low molecular weight protein which when given IV
promptly neutralizes strongly acidic heparin weight by weight.
• 1mg of protamine sulphate for 100U of heparin.
• Neutralization of LMWH by protamine is incomplete.
• Protamine cant antagonize the actions of fondaparinux.
37. • However the use of excess protamine sulphate should be avoided as itself
has an anticoagulant effect.
• Being a basic drug it releases histamine, if given by rapid IV injection,
hypersensitivity reaction, flushing and bronchoconstriction can occur.
39. • Fondaparinux sodium is a synthetic pentasaccharide that causes an
antithrombin III mediated selective inhibiton of factor Xa
• Neutralization of factor Xa interrupts the blood coagulation cascade
leading ultimately to the inhibition of thrombin formation.
• But it doesn’t cause inhibition of thrombin by itself because of shorter
polymer length.
• It is administered s.c. once daily usual adult dose 2.5mg.
40. • Bioavailability is 100 percent by this route.
• Half life is 17-21 hrs which gets prolonged in cases of renal impairment. So
dosage adjustment becomes necessary.
• It is excreted in urine.
• It has lesser antiplatelet action.
41. • And hence causes of thrombocytopenia are less frequent.
• It is generally preferred for thromboprophylaxis of patients undergoing
hip or knee surgery and for therapy of pulmonary embolism.
• Idraparinux sodium is a long acting congener of fondaparinux acts similar
to this by binding with factor Xa and is administered S.C in once weekly
doses.
45. • Thrombin is a protease inhibitor that performs a number of functions in
the haemostasis process
• 1. It proteolytically cleaves fibrinogen to fibrin.
• 2. It activates factor XIII which cross link fibrin polymer to form a stable
clot.
• 3.it activates platelets.
• 4.induces endothelial release of PGI2, t-PA and PAI-1
46. • In view of thrombin actions, DTIs would be expected to have profound
effects on coagulation.
• Majority of these agents act by binding to thrombin directly and thereby
inhibits its effects in the downstream of blood coagulation cascade.
• These drugs neither bind to ATIII nor to other plasma proteins such as
platelet factors.
48. • It is a specific irreversible inhibitor of thrombin
• It is obtained from the salivary glands of leech.
• In Hirudo medicinalis: There are reports that surgeons had used leeches
to prevent thrombosis in fine vessels in reconstruction surgery to attach
parts of limbs, digits, toes.
50. • It is the recombinant form of hirudin.
• It is derived from yeast cells.
• The binding of lepirudin to thrombin prevents the thrombin mediated
activation of fibrinogen to form fibrin.
• And factor 13 to inhibit fibrin stabilization.
• The drug has shorter half life
51. • It is administered by IV route.
• It is renally excreted.
• It is used as anticoagulants in thrombotic events associated with heparin
induced thrombocytopenia in patients of thromboembolic disease.
• Its unlabeled use is for prevention of ischemic complications associated
with unstable angina and acute MI including those undergoing coronary
stenting and percutaneous angiography and angioplasty.
• It is monitored by APTT
52. • Adverse effects include hemorrhage, hematuria and increased
transaminases.
• Patient may develop antibodies directed against thrombin lepirudin
complex.
• These antigen antibody complexes are not cleared by kidney.
• And may result in an enhanced anticoagulant effect.
53. • And may limit the long term effectiveness of agent as anticoagulant.
• There is no antidote to lepirudin.
• It is better choice for patients having hepatic insufficiency.
55. • It is another synthetic hirudin like peptide which acts as thrombin
inhibitor.
• The drug is administered by IV route.
• It has rapid onset of action with short duration 1hr t1/2-25min.
• It is used in percutaneous angiography and angioplasty as an alternative
to heparin.
• Desirudin like lepurudin blocks catalytic activity of thrombin and is used to
treat deep vein thrombosis and for prophylaxis against deep vein
thrombosis during hip replacement.
57. • It is a synthetic non peptide molecule
• It inhibits thrombin and used for prophylaxis and treatment of thrombosis
in patients with heparin induced thrombocytopenia as an alternative to
lepirudin.
• Including patients undergoing PCI percutaneous coronary intervention.
• It has a short duration of action and given by continued IV infusion with
monitoring of aPTT.
• Its clearance is not affected by renal disease.
• Hence it is a better choice for patients having renal insufficiency.
59. • It is a human recombinant activated protein C.
• It inhibits factor Va and VIIIa and thereby limit pathological thrombosis.
• It has shorter plasma half life 1.5 hrs.
• Besides its use as anticoagulant, it is given by continuous IV infusion to
decrease the mortality risk from severe sepsis associated with organ
dysfunction in adults.
• Factors contributing to such effects are not understood.
61. A) direct thrombin inhibitor:
• Dabigatran etexilate(prodrug of debigatran)
B) Director factor Xa inhibitor:
• Rivaroxaban, apixaban, betrixaban, edoxaban.
62. • A major progress in the area of anticoagulant therapy has been to develop
normally orally active thrombin inhibitors like dabigatran and novel orally
active factor Xa inhibitors like rivaroxaban, apixaban, betrixaban and
edoxaban.
• For prevention of venous thromboembolic events in adult patients who
have undergone elective total hip replacement or total knee replacement
surgery
• For prevention of stroke and systemic embolism in adult patients with
non valvular atrial fibrillation with one or more risk factors.
• The anticoagulant therapy with these agents appears to be cost effective
since no routine coagulation monitoring is essential.
63. • These have been found equivalent to LMWH in safety and efficacy.
• In future they may replace warfarin which has a narrow therapeutic
window, requires dose adjustments and exhibits potential drug
interactions.
• Both group of drugs have been approved for treatment of deep vein
thrombosis and prevention of stroke in atrial fibrillation.
65. • The novel oral anticoagulants like rivaroxaban and DTI like dabigatran although
exhibit predictable anticoagulant action and improved side effect profile, they
lack broad spectrum reversal agent.
• Pharmacological anticoagulation becomes a clinical problem when
anticoagulated patients experience major bleeding, has a traumatic injury or
requires emergency surgery.
• Such a situation demands a specific antidote to reverse the anticoagulant
effect of the concerned drug.
• Until recently no treatment was available for dabigatran associated bleeding.
• Recently idarucizumab which targets dabigatran having 350 times more
affinity than thrombin.
66. • This drug is chimeric monoclonal antibody generated from the mouse
against dabigatran which has been humanized and reduced to a fab.
• This drug is available as solution for injection filled aseptically into sterile
glass vials containing 50ml of 50mg/ml solution total 2500mg/vial.
• This agent is used by slow infusion in the doses of 1000-4000 mg in 30
minutes.
67. • Another two agents which have been developed as antidote for DFXaI is
andexanet alfa.
• Ciraparantag , a broad spectrum DTI and DFXaI anticoagulant reversal
agent.
• Both antidotes are administered by IV infusion.
70. • Introduction of dicumarol in 1940s provided new era of relatively
inexpensive, self administrated oral anticoagulant therapy.
• Since then several other coumarin derivatives have been introduced along
with other related groups called indanediones.
• Indanediones however are more toxic than coumarins and are rarely used
these days.
72. • both coumarin warfarin and its analogues and indanediones phenindione
derivatives act by competitively inhibits vitamin K reductase and
therefore inhibit the synthesis of clotting factors 2, 7, 9 and 10 by the liver.
• Vitamin K reductase converts the epoxide KO to KH which is a cofactor in
gamma carboxylation actiation of these factors.
73.
74.
75. Why their anticoagulant effects takes
1-3 days to develop?
• the concentration of factor 7 is decreased earlier t1/2- 6hrs
• the most important factor prothrombin factor 2 is the last one to be
decreased
• As the plasma half life of prothrombin is 2-3 days, the decline in the
levels of prothrombin already in plasma takes time.
76. Monitoring of warfarin
• Monitoring of coumarin and phenindione drug therapy is done by
estimation of prothrombin time in blood.
• Vitamin k antagonists donot alter bleeding time.
77. Pharmacokinetics:
• Oral bioavailability of warfarin is 100 percent.
• Over 99% of warfarin is bound to plasma proteins which results in its low
aVd
• Longer plasma half life 36 hrs.
• Several drug displacement reactions.
• It is metabolized by enzyme cyp2c9
78. • It is partly conjugated with glucuronic acid in liver.
• It undergoes enterohepatic circulation.
• It is finally excreted in urine.
• Coumarins cross placental barrier.
• But active form of drug is insignificantly excreted through milk.
79. Treatment of warfarin/phenindione
overdosage/poisoning:
• As a corollary, vitamin K1 phytonadione can be used to treat the
overdosage toxicity of coumarin/indanedione group of oral
anticoagulants.
• in milder episodes, only stopping of warfarin administration usually
suffices.
• Fresh frozen plasma or factor 9 concentrate which contains larger
amounts of prothrombin complex can also be infused.
• All such measures merely restore the normal activity of clotting factors.
81. • Enzyme inhibitors like metronidazole, chloramphenicol, disulfiram,
erythromycin, cimetidine.
• Drugs which displace warfarin from protein binding sites such as
cotrimoxazole, indomethacin, phenytoin.
• Liquid paraffin(habitual use): due to emulsification and excretion of
vitamin K which leads to vitamin K deficiency.
• Inhibitors of platelet aggregation: aspirin
82. • Drugs which inhibit gut flora and reduce vitamin K synthesis:
E.g. broad spectrum antibiotics
• Drugs causing hypoprothrombinemia such as third generation
cephalosporins like cefoperazone, cefamandole and moxalactam.
• Miscellaneous factors: hepatic disease(decrease the synthesis of clotting
factors)
• Hyperthyroidism enhances catabolism of clotting factors.
83. Wafarin activity is reduced by
concomitant use of
• Enzyme inducers: barbiturates, rifampicin, griseofulvin and
carbamazepine.
• Drugs that bind to warfarin and inhibit its absorption: cholestyramine and
sucralfate.
• Drugs that increase the synthesis of clotting factors: E.g. estrogen
containing oral contraceptive pills.
• Miscellaneous factors:
• Hypothyroidism(reduced catabolism of clotting factors)
• Hereditary resistance: mutational changes in vitamin K reductase enzyme
84. • Contraindications: warfarin should not be used during pregnancy because
it may cause abortion as well as birth defects CONTRADI SYNDROME.
85. Warfarin dose adjustment
• INR < 1.5 - Increase dose by 15% retest after 1 week
• INR >1.5 - <2 – increase by 10 % retest after 1 week
• INR 2-3 – no change
• INR 3 - <4 – decrease by 10 percent retest after 1 week.
• INR 4- <5 – hold dose for one day, then decrease by 10 percent. Retest after 3
to 7 days
• INR 5- <8 – hold dose until INR is therapeutic then decrease by 15% . Retest
after 2 days.
• If INR is >5 there is high risk of bleeding, or if the INR >8, administer 1-5mg of
vitamin K orally.
87. • Anticoagulants donot dissolve the clot that has already been formed.
• But they prevent the thrombus extention, recurrence and embolic
complications by reducing the rate of thrombin formation.
• Heparin is used initially for its rapid onset of action.
• While an oral anticoagulant is usually started concurrently.
• Heparin is then discontinued after 6-7 days when the warfarin has taken
its full therapeutic benefits.
88. 1. Prevention and treatment of deep
vein thrombosis and pulmonary
embolism:
89. • Venous thrombi are generally fibrin thrombi and hence anticoagulants are
very effective in such situations.
• Prophylaxis is usually needed for bedridden patients, old, postoperative
cases and for patients with hip/leg fracture.
• For prophylaxis intermittent low dose heparin administration 5000IU s.c,
8-12th hrly is generally preferred.
• LMW heparin enoxaparin 30mg SC 12th hrly or dalteparin 5000U S.C per
day.
90. • The main advantage of LMWH over standard heparin is its
S.C.administration without laboratory monitoring with minimal risk of
thrombocytopenia, osteopenia and spontaneous bleeding.
• For an established venous thrombosis, a bolus IV injection of 5000-
10000U of heparin is given followed by IV infusion of 1000U/hr.
• Heparin is used for 6-7 days followed by warfarin with a 3 days overlap
period.
• Treatment with warfarin is usually started with 10-15mg orally per day
with a check on prothrombin time.
91. • The aim is to reduce plasma thrombin activity to 25% of the normal value.
• Once the objective has been achieved, a maintenance dose of 5-7mg/day
can be given.
• Warfarin may soon be replaced by oral thrombin inhibitor dabigatran and
oral Xa inhibitor rivaroxaban.
93. • arterial thrombi are primary platelet thrombi, hence the antiplatelet
drugs are more effective than anticoagulants.
• However these can be used to reduce secondary thromboembolic
complications.
• LMWH can be given for short periods till patients become ambulatory.
• They may also be used during coronary angioplasty and stent
replacement.
95. • to reduce the chances of MI in unstable angina.
• Aspirin + heparin followed by warfarin can be used.
96. • Rheumatic heart disease: if there are chances of thrombosis or embolism
from atrial fibrillation.
• Warfarin, low dose heparin, low dose aspirin can be used to prevent the
chances of stroke.
• However warfarin is more effective in atrial fibrillation patients with high
risk of stroke.
• While aspirin is reserved for low risk patients or those who cant take
warfarin.
• Cerebrovascular diseases: use of antiplatelet drug is more safe, simpler
and efficaicious than the use of oral anticoagulants.
98. 1. Treatment of DIC.
2. Treatment of peripheral retinal vessel embolism.
3. During cardiac bypass surgery and in placing artificial heart valves to
prevent formation of any thrombus/emboli.
4. To prevent clotting in extracorporeal circulation, during hemodialysis.
100. • In contrast to warfarin, heparin doesn’t cross placenta and is not
associated with foetal malformation.
• Hence heparin is preferred for such indication.
102. • Hemorrhage is the commonest adverse effect.
• Chances of hemorrhage are more in presence of renal or hepatic
impairment due to reduced rate of elimination.
106. • Teratogenic effects CONTRADI SYNDROME
• It crosses placenta
• Leads to hemorrhagic disorders in foetus and foetal bone deformities.
• Transient alopecia
• Dermatitis and diarrhea.
108. • Bleeding disorders
• Thrombocytopenia
• Severe hypertension risk of cerebral hemorrhage.
• Threatened abortion.
• Bleeding piles.
• Subacute bacterial endocarditis chances of embolism.
• Tuberculosis chances of hemoptysis.
• Concurrent use of aspirin and other antiplatelet therapy.
109. • For warfarin therapy: same as for heparin plus
• Pregnancy: it increases chances of birth defects specially skeletal
abnormalities.
• Necrosis of soft tissues buttocks and breast shortly after the start of
warfarin therapy.
110.
111. Reason for skin necrosis by warfarin.
• Warfarin like inhibitting clotting factors 2,7,9,10 also inhibits anticoagulant
factors protein C and S.
• The half life of protein C is just 8 hrs so it can lead to thrombotic
complication in soft tissues very early as inhibiting the anticoagulant lead
to opposite thrombotic effects.
113. • It occurs due to the formation of antibodies against complexes of heparin
with platelet factor 4, which results in paradoxical thrombosis.
• Most specific diagnostic test for HIT is serotonin release assay.
• Warfarin and LMWH are contraindicated.
• Anticoagulant of choice is direct thrombin inhibitors like lepirudin and
bivalirudin. Fondaparinux can also be used.
114. Features of HIT
• Platelet count less than 150000/ul or decreased by >50%.
• Starts 5-10 days after starting heparin.
• More common with unfractionated heparin than LMWH heparin.
• Surgical patients than medical patients
• Female than males
• Venous thrombosis than arterial
• Bilateral adrenal hemorrhage and skin lesions
115. Management of HIT
• Stop all forms of heparin and LMWH.
• Don’t give platelet transfusion.
• DTI should be given.
• Lepirudin safe in liver failure and argatroban safe in renal failure patients.
• Warfarin not given initially as it causes hypercoagulability.
• Lepirudin continued till platelet count reaches 1 lakh/ul.
• Now warfarin started and DTIs discontinued.
• Warfarin should be given for atleast 30 days.