Fibrinolytic agents are plasminogen activators(PA) that act by converting plasminogen to plasmin. Plasmin then degrades the fibrin matrix of thrombi and produces soluble fibrin degradation products resulting in clot lysis.
PAs that preferentially activate fibrin-bound plasminogen are fibrin-specific. Nonspecific PAs do not discriminate between fibrin-bound and circulating plasminogen. Activation of circulating plasminogen generates unopposed plasmin & can trigger a systemic lytic state.
Fibrinolytics are used for intravenous thrombolysis(IVT) in ST Elevation MI, Massive Pulmonary embolism, and Acute Ischemic stroke. Peripheral arterial thrombi and thrombi in the proximal deep veins of the leg are most often treated using catheter-directed thrombolytic therapy.
Indications and contraindications are to be throughly vetted before considering fibrinolytic therapy owing to their propensity to cause hemorrhage.
Urokinase is not prefered. Aanistreplase is costly to manufacture and is not commonly used. Only nonspecific fibrinolytic used is streptokinase that too not commonly. It is still used because it has mortality benefit in MI and is cheap compared to fibrin specific fibrinolytics.
IVT in STEMI:
Primary PCI is the preferred mode of reperfusion in a PCI-capable facility. For IVT, bolus fibrinolytics (Tenecteplase) are preferred as there is ⬇️chance of medication errors and are associated with ⬇️ noncerebral bleeding and has potential for prehospital Rx
For Thrombolysis in STEMI the treatment time window is within 30min to up to 12hrs of onset of symptoms. Best results if given within 1-2 hrs.
Thrombolysis in Acute Ischemic Stroke (AIS):
Eligible patients should receive thrombolysis as soon as possible, ideally within 60 minutes of hospital arrival. Only Alteplase and Tenecteplase are recommended for IVT in AIS.
Thrombolysis in pulmonary embolism (PE):
Patients with massive PE or high-risk submassive PE (with both right ventricular dysfunction and troponin elevation due to right ventricular injury) are candidates for IVT.
Patients who receive thrombolysis up to 14 days after onset of new symptoms or signs in PE can derive benefit, probably because of the effects on the bronchial collateral circulation.
There is a 1% to 3% rate of intracranial hemorrhage in patients with PE receiving full-dose IVT. Off-label half dose of alteplase(50mg) infusion over 2hrs is sometimes used to mitigate the risk of bleeds. Catheter-directed pharmacomechanical therapy has lower rates of bleeding.
Source
1.Harrisons Principles of Internal Medicine, 21e
2.Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 11e
3.2021,European Stroke Organisation (ESO) guidelines on intravenous thrombolysis for acute ischaemic stroke
"Doctor, my vitamin D levels are only 9. I am always tired"
Frequent scenario in my clinic and this is how I approach this . A🧵
1,25(OH)2 VitD is the active form of vitD in our body. But the levels of 1,25(OH)2 is almost always normal in vitD deficiency. This is why we doctors always recommend checking serum levels of 25(OH) vitamin D to evaluate vitamin D deficiency.
You see, 25(OH) vitamin D is the primary form that circulates and gets stored in your body. On the other hand, levels of 1,25(OH)2 vitamin D, which is the active form, are seldom requested by physicians because they're not meant for diagnosing deficiency. Instead, they're useful for investigating elevated calcium levels due to conditions like granulomatous diseases, but let's keep our focus on vitamin D deficiency for now. Most crucially, remember that 1,25(OH)2 assays are available in labs, so avoid mistakenly ordering them just to screen for vitamin D deficiency.
I want to ascertain something here. There are myriad causes of tiredness, and I will not jump the gun here just by seeing a low serum vitamin D report and calling it. I would definitely rule out other causes of fatigue, but now will stick to vitamin D deficiency for the sake of our discussion here. Read on….
Vitamin D deficiency is mainly diagnosed by measuring serum 25-hydroxyvitamin D (25(OH)D), the key biomarker for vitamin D status, as it reflects skin production, diet, and supplementation effects.
Thresholds generally classify deficiency below 20 ng/mL (50 nmol/L), insufficiency at 20-30 ng/mL (50-75 nmol/L), and sufficiency at 30-50 ng/mL (75-125 nmol/L), though these lack full agreement and stem from observational studies rather than trials.
Routine checking isn't recommended for symptom-free people, but it's advised for high-risk groups like those with malabsorption, chronic kidney disease, obesity (BMI >30 kg/m²), dark skin, low sun exposure, or symptoms such as bone/muscle pain.
🔸Why is vitamin D important to our body?
Vitamin D plays a pivotal role in regulating calcium and phosphorus homeostasis by enhancing their intestinal absorption, promoting renal reabsorption, and supporting bone mineralization, which helps prevent conditions like rickets in children or osteomalacia/osteoporosis in adults. It also modulates your immune response by fine-tuning immunity, potentially reducing susceptibility to infections and chronic inflammation. On top of that, its pleiotropic effects extend to cardiovascular protection and lowering all-cause mortality, while optimizing maternal-fetal outcomes during pregnancy through various signaling pathways in cells.
🔸What causes vitamin D deficiency?
There are many causes of low vitamin D levels in the body. Here, I am strictly sticking to nutritional and lifestyle-related causes to avoid the risk of overwhelming you.
Older people often ask me this question: "Vitamin D deficiency was not common in our times. Why is it so common now? What changed?
Well, the short answer is nutritional choices and low sun exposure. You can understand this answer if you compare your lifestyle and food choices with the older generation.
🔸How does our body get vitamin D?
Vitamin D is more of a hormone than a vitamin if you have understood its action. The body is capable of creating its own vitamin D in the skin if it gets exposed to UV rays. When the skin is exposed to UV rays, an intermediate of cholesterol metabolism called 7-dehydrocholesterol, which is present in the skin cells, gets converted to vitamin D3 (cholecalciferol). This vitamin D3 then gets hydroxylated in the liver and finally in the kidneys to form the active form, 1,25(OH)2 vitamin D. Medical societies have come to the conclusion that merely sunlight exposure may not be enough for meeting the daily vitamin D requirements. Read on....
The other source of vitamin D is from the diet. It is obvious that if the diet is not proper and there is low sunlight exposure, the chances of vitamin D deficiency increases, as the daily recommended intake is 600-800 IU/day. So, supplementation may be required.
So by now, you have become familiar with the various forms of vitamin D.
A 🧵 on chest Xray signs in pulmonary thromboembolism.
The 𝗙𝗹𝗲𝗶𝘀𝗰𝗵𝗻𝗲𝗿 𝘀𝗶𝗴𝗻 is a prominent central artery that can be caused either by pulmonary hypertension or by distension of the vessel by a large pulmonary embolus seen on chest x ray.
𝗛𝗮𝗺𝗽𝘁𝗼𝗻 𝗵𝘂𝗺𝗽 refers to a dome-shaped, pleural-based opacification in the lung most commonly due to pulmonary embolism and lung infarction (it can also result from other causes of pulmonary infarction (e.g. vascular occlusion due to angioinvasive aspergillosis)
💥Smith 𝘦𝘵 𝘢𝘭. reported draining a world record of 41 𝗹𝗶𝘁𝗿𝗲𝘀 of ascitic fluid in a single paracentesis session of a patient with decompensated cirrhosis.
How much Albumin would be needed in this case to prevent post paracentesis circulatory dysfunction ? 🧵 Read on👇
A 🧵 on important points to consider while performing Large Volume Paracentesis (LVP)
🛑Large Volume Paracentesis(LVP)
is arbitrarily defined as a paracentesis with >5 L of ascitic fluid drained.
In patients undergoing LVP, the use of albumin is crucial to prevent a further reduction of effective arterial blood volume, which may precipitate postparacentesis circulatory dysfunction (PPCD).
The clinical manifestations of PPCD include renal impairment, including HRS, dilutional hyponatremia, hepatic encephalopathy and death.
Albumin infusion is particularly important if more than 5 L of ascites are removed to prevent the development of PPCD.
Paracenteses of a smaller volume(<5L) are not associated with significant hemodynamic changes and albumin infusion may not be required.
Although there has not been a dose‐response study on albumin use with LVP, the administration of 6‐8 g of albumin per liter of ascites removed has been recommended.
💥For example, after the fifth liter, approximately 40 g of albumin should be infused, and after 8 L removal, the amount of albumin given should be approximately 64 g.
It has been held that there is no limit for the amount of ascites that can be removed in a single session, provided an appropriate amount of albumin is administered.
However, the risk of PPCD increases with >8 L of fluid evacuated in one single session.
A study showed that by limiting the LVP volume to <8 L per session and providing a higher than recommended dose of albumin (9.0 ± 2.5 g per liter of ascites removed), renal function and survival may be better preserved over a mean period of 2 years despite the development of PPCD in 40% of patients.
In patients with hemodynamic instability (systolic blood pressure <90 mm Hg), hyponatremia (serum sodium <130 mmol/L), and/or the presence of AKI, albumin infusion should be strongly considered for paracentesis of a smaller volume.
LVP is a safe procedure even in the presence of coagulopathy. In a study that included patients with an international normalized ratio of >1.5 and a platelet count of <50 × 109/L, only 1% of patients experienced minimal cutaneous bleeding after LVP.
Therefore, elevated prothrombin time or thrombocytopenia is not a contraindication for paracentesis, nor is transfusion of clotting factors or platelets recommended.
Possible exceptions may include patients with disseminated intravascular coagulation or uremia with thrombocytopenia.
1/3 👇 𝘾𝙤𝙣𝙩.
💥Ideal site for needle insertion in abdominal paracentesis