Dactylitis vs Sclerodactyly

 

Red blood cell transfusion thresholds mnemonic

 Hello everyone! Just look here.. 

What does it mean ? SHOAN …? 

the name Shoan is of Hebrew origin and means "Gift of Salvation". 

That’s all!

Thank you! 🩺🫀

Direct oral anticoagulants (DOACs) dosing for stroke prevention in atrial fibrillation mnemonic

Hi everyone!

Here are some DOAC dosing mnemonics for atrial fibrillation! 

RivarOxaban: Once daily

Apixaban: Twice daily 

Dabigatran: Twice daily

EdOxaban: Once daily

Mnemonic: Drugs with O have Once-daily dosing. 

Rivaroxaban: 20 mg once daily with the evening meal (creatinine clearance [CrCl] >50 mL/minute); or 15 mg once daily with the evening meal (CrCl ≤50 mL/minute).

Mnemonic: R without the straight line | looks like 2 to me for 20 mg!

Apixaban: 5 mg twice daily (CrCl >50 mL/minute); or 2.5 mg twice daily for those with any two of the following: age ≥80 years, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL.

Mnemonic: Apixa has 5 letters for 5 mg!

Dabigatran: 110 mg BID or 150 mg BID (CrCl >30 mL/minute).

European labeling suggests dose reduction in patients older than 75 years (eg, 150 mg orally once per day or 110 mg orally twice per day).

Edoxaban: 30 mg (weight ≤60 kg) or 60 mg (weight >60 kg) orally once daily.

That's all!

Remember that the dosing varies for VTE treatment and prophylaxis so do not apply these mnemonics for VTE.

-IkaN

Formulation, absorption and associated side effect of dabigatran

Did you know that the absorption of dabigatran etexilate is dependent on an acid environment in the stomach?

This is why it is formulated together with tartaric acid pellets. These pellets provide an acidic environment, which increases drug dissolution and absorption, regardless of variations in gastric pH. This is also why the absorption is not affected by the coadministration of a proton pump inhibitor.

A lower pH is associated with dyspepsia, esophagitis, and plays a part in the increased risk of gastrointestinal bleeding.

-IkaN

Why von Willebrand disease has normal aPTT sometimes ?

VWF acts as a carrier protein for factor VIII.  Factor VIII is more rapidly degraded when unbound, and VWF deficiency can therefore lead to impairment of the intrinsic coagulation pathway leading to a prolonged activated PTT.  

Fact- Reversible ADP-r inhibitors cause breathlessness

Hi

 Reversible inhibitors of ADP-r (P2Y12) such as ticagrelor, cangrelor, and elinogrel used as anti-platelet drugs have a unique side effect of dyspnea, unlike the irreversible ones. This is hypothesized to occur because of reversible inhibition of ADP-r on sensory neurons. Since half-life of the reversible inhibitors is shorter than that of irreversibles, repeated doses lead to permanent inhibition of the P2Y12 receptors on sensory neurons.

 Moreover, oral administration is found to cause more severe effects on the breathing difficulties than the parenteral route.

 Source- Research gate 

 

That's  all

- Jaskunwar Singh

Sickle cell retinopathy

 What is the hallmark of sickle cell retinopathy?

Sea fan neovascularization.

All patients with SCD should have dilated funduscopic examinations every 1 to 2 years beginning at age 10, preferably by a retina specialist.

Treatment is usually Laser photocoagulation.

Anti-VEGF medications such as bevacizumab or ranibizumab may lead to partial regression of sea-fan neovascularization.

Sickle cell anemic retinopathy is seen mostly in heterozygous S-C trait and S-Thal trait. 

Fun fact: Sea fans are beautiful soft corals.

-IkaN

COVID-19 and Vasculopathy

Over the past few months, overwhelming evidence has accumulated suggesting the dysregulation of the coagulation pathways in COVID patients stemming from the altered immune and inflammatory response towards SARS-CoV2.

Observed coagulation abnormalities have multi-faceted pathogenesis. The most likely suspect is microvascular dysfunction secondary to cytokine storm-like state, tipping the balance towards thrombosis. Direct vascular injury is also likely with evidence of endothelial viral inclusions in some cases.

-Pulmonary Intravascular Thrombosis

Evidence suggests that starking discrepancy exists between hypoxemia onset and respiratory failure in COVID patients, with the former occurring fairly early in the disease course, pointing to the fact that it's not classic ARDS-like pathology that is responsible for the marked deterioration in the pulmonary gas exchange process. It is appropriately explained by the diffuse thrombosis affecting the pulmonary vasculature. In fact, it's so prominent that a whole new entity called "Pulmonary Intravascular Thrombosis" has been proposed as the framework for explaining this phenomenon.

Pulmonary Intravascular Thrombosis could be considered as lying along the spectrum of classic DIC with few important dissimilarities. It is usually localized to the pulmonary vascular bed at least initially and doesn't feature hypofibrinogenemia, consistent with the acute phase response driving continued fibrinogen production. D-dimers levels, however, are significantly elevated suggesting thrombus formation and ongoing hyperfibrinolysis.

-Pathogenesis

ACE2 is expressed in huge numbers on the alveolar epithelial cells, especially type 2 cells and also pulmonary endothelial cells. Hence, in contrast to patchy involvement classically seen in bronchopneumonia, in COVID, extensive involvement of the alveolo-capillary network is seen. This, in turn, results in florid interstitial inflammation resulting in efflux and activation of macrophages in the alveoli. It is so rampant that it has been likened to Macrophage Activation Syndrome (MAS) or sHLH like state. Activated epithelial cells and macrophages then orchestrate the cytokine storm leading to microvascular dysfunction and widespread thrombosis in the juxtaposed capillary network. Enhanced tissue factor and thrombin expression, coupled simultaneously with the reduced levels of PAI-1 drives thrombosis. Hypoxemia due to V/Q mismatch further exacerbates this process.

Levels of ACE2 in alveoli initially decrease as the virus particles are internalized. ACE2, by virtue of its ability to convert AngII to anti-inflammatory Ang1-7 peptide, keeps excessive inflammation in check. Hence, reduced ACE2 expression compounds the thrombotic propensity in the vascular bed. Direct involvement of endothelial cells by virus leading to endothelitis/vasculitis has also been suggested, although endothelial activation due to inflammatory cytokines seems more likely.

Reduced type 1 interferon signaling pathways are another intriguing possibility contributing to hyperinflammation. The role of positive pressure ventilation in forcing the viral particles and cytokines in vasculature also merits consideration.

- Skin manifestations

A variety of skin manifestations ranging from pseudo-chilblains to livedoid lesions have been described in COVID patients. While some of the lesions, like acral vesicles and pustules, confer to the pattern of viral exanthem, livedoid lesions suggest the possibility of vascular injury. These vasculopathy eruptions are known as "toevids", appearing as violaceous plaque-like eruptions over toes. Upon molecular testing, such patients often are negative, suggesting that they have probably cleared the infection and vascular injury is perhaps immune-mediated.
Interestingly, papular gloves and socks syndrome, occasionally seen in association with viral infections, especially Parvovirus, bears substantial similarity to certain COVID lesions, both clinically and histologically, with some reports even documenting evidence of leukocytoclastic vasculitis in the former.



-Clinical Relevance

Significant elevations in pulmonary pressures due to diffuse thrombosis strains the right ventricle causing hemodynamic dysfunction. Elevated D-dimer, pro- BNP, and troponin levels have been proven to be poor prognostic markers consistently across various studies. The development of an overt DIC-like state certainly portends a dismal prognosis.

Troponinemia in COVID can be attributed to severe right ventricular strain in the setting of pulmonary embolism and/or Pulmonary Intravascular Thrombosis. Some evidence also exists regarding the possibility of myocarditis, however, without classic lymphocytic infiltration characteristic of viral myocarditis.



To summarize, the intricate interplay of diffuse pulmonary intravascular thrombosis and MAS-like state drives the severe and often fatal pulmonary microvascular dysfunction in COVID.

SARS-CoV2 infection--> diffuse alveolar damage--> interstitial inflammation--> MAS like state--> massive activation of macrophages--> local inflammatory cytokine milieu--> Microvascular dysfunction--> Pulmonary  Intravascular Thrombosis

-Kirtan Patolia


Reference:

1.) https://doi.org/10.1016/S2665-9913(20)30121-1
https://www.thelancet.com/journals/lanrhe/article/PIIS2665-9913(20)30121-1/fulltext

2.) https://doi.org/10.1111/bjd.19163
https://onlinelibrary.wiley.com/doi/abs/10.1111/bjd.19163

COVID-19: Lymphopenia and pneumonia

Hello everyone!

In the context of COVID-19, we will talk about two specific terms: Lymphopenia and Pneumonia.

COVID-19 Pneumonia
We mention "pneumonia" when there is an acute inflammation of the lungs following an infection. Pneumonia is one of the common features in infected patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pneumonia has various clinical and radiological characteristics depending on the stage of the disease. It evolves rapidly, even in asymptomatic patients from local unilateral to diffuse bilateral ground-grass opacities which progress within 1-3 weeks to consolidation or co-exists with. A retrospective study at Wuhan describes radiological findings from 81 patients with COVID-19 pneumonia. The predominant pattern of abnormality observed was bilateral (79%), peripheral (54%), ill-defined (81%) and ground-glass opacification (65%), mainly involving the right lower lobes. [1]

Acquired coagulopathy

Apart from congenital disorders, various clinical scenarios can give rise to altered hemostatic patterns leading to the state of so-called "acquired coagulopathy".

1.) Due to Factor inhibitors:
Classically it is seen in pregnant patients and those with lymphoproliferative disorders like CLL. However, it could be idiopathic.
Usually, it leads to the acquired factor Vlll and V deficiency.

Mixing studies are employed to differentiate between acquired and congenital factor deficiency. Failure of correction of clotting assays after mixing studies suggests the presence of inhibitors.

2.) Amyloidosis
Sequestration of Factor X by amyloid fibrils leads to an acquired deficiency-like state. Amyloid vasculopathy along with factor X deficiency often leads to purpura and ecchymosis in these patients.

3.) Myeloproliferative neoplasms
Apart from acquired vWD due to loss of HMW vWF multimers, acquired factor V deficiency can also be seen. This has been attributed to adherence of Factor V to megakaryoblasts similar to the relation between factor X and amyloid fibrils. However, severe clinical manifestations might not necessarily reflect upon clotting assays or factor levels with the latter suggesting functional factor V deficiency.

3.) Thrombotic microangiopathies and DIC
Usually leads to both thrombotic and bleeding manifestations. The spectrum of TMA includes HUS, aHUS, TTP, HELLP syndrome, DIC, cAPLA, scleroderma renal crisis, malignant hypertension, and radiation or HSCT-induced vasculopathy.

4.) Coagulopathy of liver failure
Classically seen in the setting of fulminant liver injury which may be due to the infections, drugs, autoimmune hepatitis, ischemic hepatitis/shock liver, or rarely in Wilson's disease due to massive hepatocyte destruction.
One of the hallmark lab findings includes normal factor VIII levels. This is due to the fact that factor VIII, unlike other factors, is chiefly produced by endothelial cells rather than by hepatocytes. In fact, due to its reduced metabolism by hepatocytes in the state of liver failure, factor VIIl levels are often elevated.

Other miscellaneous causes include Acute fatty liver of pregnancy, fat embolism syndrome, amniotic fluid embolism, and other pregnancy-associated complications.

- Kirtan Patolia

Acquired Von willebrand disease

Von Willebrand disease is one of the most commonly encountered congenital bleeding disorders in clinical practice. Broadly speaking they are classified as type 1, 2A, 2B, 2M, 2N, and 3. Each one of them is distinct from the other in subtle ways.

However, it could be acquired in a number of ways.

 a.) In patients with thrombocytosis > 1 million cells/ microliter, especially in essential thrombocythemia, loss of HMW  vWD multimers leads to reduced vWF Ristocetin activity: vWF antigen ratio (<0.6)  suggesting type 2 like pattern.

 b.) In patients with aortic stenosis, due to extreme shear stress, vWF unfolds prematurely at the site of the valve revealing ADAMTS13 binding sites, ultimately resulting in its cleavage and loss of HMW multimers. So basically, it could be visualized as the pattern that is just opposite to TTP wherein defective ADAMTS13 activity results in excess of HMW vWF multimers.

It is often associated with either angiodysplasia or AVMs of the GI tract that further predisposes to bleeding. Although the exact pathogenesis of these lesions is not understood, one postulated mechanism suggests chronic colonic ischemia leading to sympathetic nervous system-induced vasodilation as a potential culprit.
 In this context, it is also known as Heyde's syndrome.

c.) Sometimes in severe hypothyroidism, often the production of vWF by endothelial cells itself is markedly reduced.

d.) Rarely in the setting of multiple myeloma and various other neoplasms, tumor cells express the excess of Gpllb/llla leading to enhanced clearance of vWF from circulation.

One of the common lab findings in acquired vWD is reduced vWF Ristocetin activity: vWF antigen ratio pointing to the disproportionate decrease in activity compared to antigen levels.
It is due to the loss of HMW  multimers.

- Kirtan Patolia

Spherocytosis

Hello Awesomites !

The future blogs will be on confusers.

Q. On peripheral blood smears there is presence of spherocytes. What are the differentials and the test to identify the same?

Most of you have prompted it as hereditary spherocytosis.
 Let see.

Ans. DIFFERENTIALS :- 

• HEREDITARY SPHEROCYTOSIS
• AUTO-IMMUNE HEMOLYTIC ANEMIA

 Best next step is to do DIRECT COOMBS TEST to rule out autoimmune hemolytic anemia.
For hereditary spherocytosis go for osmotic fragility test.  


 So spherocytosis doesn't means Hereditary, it could be acquired, usually preceded by an infection.

HAPPY STUDYING :) 
-Upasana Y.

Therapeutics in Sickle Cell Anemia

Apart from Hydroxyurea, Analgesics and vasodilators like phosphodiesterase inhibitors, certain tantalizing novel drugs have been approved for Sickle cell anemia.... Let's take a closer look at them.

(1) Voxelotor (HbS polymerization inhibitor) binds covalently to N-terminal valine of alpha chain of HbS (around 30% of HbS in individual cell) stabilizing it's oxygenated form and causing left ward shift of dissociation curve without impairing oxygen delivery to tissues.

Consistently reduces hemolysis and viscosity with in 2 weeks of administration... FIRST EVER therapy targeting core defect.

Cryoprecipitate

Hey! =)

What does cryoprecipitate contain? 
Cryoprecipitate preparations contain concentrated amounts of fibrinogen (factor I), factor VIII (antihaemophilic factor), von Willebrand factor, factor XIII (fibrin-stabilizing factor), and fibronectin.

Why is it called cryoprecipitate?

Multiple Myeloma notes and mnemonics

Hi!

Multiple myeloma - everything P

- malignant Proliferation of Plasma cells derived from a single clone.

- Immunoglobulin produced is a "ParaProtein" (M- protein)

- POEMS syndrome

BONE MARROW INVOLVEMENT

- Pancytopenia

PERIPHERAL BLOOD

- plasma cell leukemia ( greater than 2,000 per mm3 )

BONE INVOLVEMENT

- punched-out lesions in radiographs of flat bones

- bone pain

- pathological fractures

RENAL INVOLVEMENT

- Bence -Jones proteinuria

- production of excess Amyloid protein

- hyPer- calci -emia and -uria

These three result in renal damage and renal failure.

IMMUNE SYSTEM INVOLVEMENT

- prone to infections, particularly in respiratory and urinary tract.

HYPERVISCOSITY SYNDROME

( mnemonic - HPRVSCST )

- Headache

- Postural hypotension

- Retinal venous congestion

- Vertigo

- Strain (blurred vision)

- Congestive cardiac failure

- subtype IgA

- nysTagmus

CLOTTING PROBLEMS

- purpura

- profuse bleeding ( epistaxis, gastrointestinal )

NEUROLOGICAL MANIFESTATIONS

- peripheral neuropathy

- compressive myopathy

- carpal tunnel syndrome ( nerve entrapment)

- Amyloidosis.

SERUM STUDIES

- total serum protein raised

- low albumin

- high globulin ( decreased A:G ratio )

- high beta-2 microglobulin ( greater than 5.5 mg/dL means poor prognosis; stage III)

Plasmacytomas in Paraskeletal soft tissues - poor prognosis; treated by palliative radiotherapy.


That's all
Anything more to add, you're most welcome :)
- Jaskunwar Singh

Protein gap

The gamma gap aka paraprotein gap or protein gap is the difference between total serum proteins and albumin measured from a comprehensive metabolic panel.

Albumin accounts for the majority of total serum protein.

Viral infections, plasma cell malignancies, or autoimmune conditions there is an excess of immunoglobulins, raising the total amount of serum protein independent of albumin.

The gamma gap is typically considered to be elevated if it is above 4 g/dL.

In the right clinical context, gamma gap should be worked up with SPEP, UPEP, and a serum free light chain assay.

Random exercise: Calculate the protein gap.
Total protein 8.9 g/dL (normal 6.4-8.3 g/dL)
Albumin is 3.6 g/dL (normal 3.4-4.8 g/dL)

That's all!

-IkaN

Diagnosing the cause of polycythemia

Polycythemia refers to an increased hemoglobin concentration and/or hematocrit in peripheral blood.
For Diagnosing the specific cause of polycythemia follow these 3 steps:

STEP1: First check for RBC mass
1)Elevation of Hgb and/or Hct due to a decrease in plasma volume alone (ie, without an increase of the RBC mass) is referred to as relative polycythemia.

2)An increase of RBC mass refers to Absolute polycythemia. It can be categorized as either primary or secondary polycythemia.

STEP2: To diagnose the causes of absolute polycythemia. Check for EPO levels
1)Primary polycythemia is caused by a mutation in RBC progenitor cells that results in increased RBC mass. So there is a decrease in EPO levels. Ex: polycythemia vera (PV)
2)Secondary polycythemia refers to an increase of RBC mass caused by elevated serum EPO. Most often, this is due to an appropriate physiologic response to tissue hypoxia, or by autonomous EPO production(eg, an EPO-secreting tumor) 

STEP3: To diagnose the causes of secondary polycythemia. Check PaO2 and SaO2 levels
1)If PaO2<65% and SaO2<92% then it is because of chronic hypoxia due to high altitude, COPD, Smoking, etc.
2)If PaO2 and SaO2 levels are normal then consider EPO-secreting tumor(renal cell carcinoma, pheochromocytoma).

-Srikar Sama

Difference Between Solitary and Singular Brain Metastasis.

Hello Guys!

So we were operating on a metastatic brain lesion the other day when My Consultant happened to ask me the question-  " What is the difference between Solitary and Singular Brain Metastasis?" Well I happened to have a vague idea and managed to blabber something, the actual definition goes as-

• A solitary brain metastasis is defined as the only known metastasis of a tumour in the whole body which happens to be
localised in the central nervous system.

• A singular brain metastasis is defined as a single cerebral metastasis with additional metastases in other organ systems.

Well it's a small nugget, may save you some embarrassing moments.

Let's Learn Together!
-Medha Vyas.

Paroxysmal nocturnal hemoglobinuria

1)PNH originates from an acquired mutation ( frame-shift that creates a premature stop codon) in a myeloid stem cell, the acquired mutation in PNH occurs in the PIGA gene which is responsible for the first step in the synthesis of the GPI anchor that attaches CD55 and CD59 to the cell surface.

2)Complement detects self vs nonself cells by these complement inhibitors. Function of these complement inhibitors is to:

3)In the absence of these inhibitors, complement proteins bind cell membranes of our own cells and through the alternative complement pathway can lyse self-cells.

4)CD55/DAF decrease → More C3 convertase→Increase C3b→Increase opsonization→Extra Vascular Hemolysis.

   CD59/MIRL decrease→More MAC→Intra Vascular Hemolysis.


5)Why nocturnal hemoglobinuria- hemolysis occurs throughout day but its more at night because:   (a)Increased hemolysis in night due to respiratory acidosis(Shallow breathing).
 (b)Overnight concentration of urine is more and hemoglobinuria is clearly evident.

6)Diagnosis:(a)Flow cytometry- decrease CD55 and CD59 levels.
                     (b)HAM test-confirmatory.
                     (c)Direct coombs test-Negative (Helps to differentiate PNH and AIHA- its positive in AIHA)                                                                           

7)Treatment: 

(a)Ravulizumab- long acting C5 complement inhibitor

(b)Eculizumab- It is an Antibody to C5 and prevents its clevage to C5a and C5b, so no MAC. Ravulizumab has a half life that is three to four times longer than eculizumab.

-Srikar Sama

SOURCE: UpToDate, Uworld.

Warfarin Induced Skin Necrosis

Warfarin-induced skin necrosis is a complication of warfarin therapy in which the patient develops demarcated areas of purpura and necrosis of skin including the extremities, breasts, trunk, or penis.

Mechanism:
1)Mechanism of action of Warfarin is it inhibits VitK epoxide reductase,so there is decrease in synthesis of VitK dependent factors - (factors II, VII, IX, and X) and natural anticoagulants (protein S and protein C).


2)Now no new clotting factors are produced but the old circulating clotting factors are still present (warfarin has no effect on already circulating clotting factors).


3)Among the factors II, VII, IX, X, ProteinC that are already present,ProteinC has the shortest half life,So ProteinC is depleted more rapidly than the others.


4)Now there is no anticoagulant in the body to oppose the action of already present clotting factors,so there will be initial coagulation till factors II, VII, IX, X gets depleted i.e till their half lives are completed.


5)This initial coagulation occurs in dermal vasculature which causes Skin Necrosis.

Prevention:
Overlapping of warfarin with heparin during the first several days of warfarin administration(if Heparin is given along with warfarin, this prevents functioning of circulating factors since heparin inhibits the activity of circulating thrombin and factorXa) and then warfarin is continued for long term therapy.


Source: UpToDate, First Aid.

-Srikar Sama