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Lisa Klimas

I'm a 35 year old microbiologist and molecular biologist with systemic mastocytosis, Ehlers Danlos Syndrome, Postural Orthostatic Tachycardia Syndrome, Adrenal Insufficiency, and an assortment of other chronic health issues. My life is pretty much a blast.

Mood disorders and inflammation: High cortisol and low serotonin (Part 2 of 4)

There are multiple suspect pathways for causation of mood dysregulation in the setting of inflammation. One well described model hinges upon the ability of inflammatory mediators to impact the HPA axis, a system of hormone release that drives many physiologic functions in addition to the stress response.  Briefly, the central pathway of the HPA axis is that CRH causes production of ACTH, which causes production of cortisol, a stress hormone and a very potent anti-inflammatory under most circumstances.  Many molecules can affect the signaling of the HPA axis and contribute to inappropriate hormone regulation.

IL-1, IL-6, TNF and IFN-a are all inflammatory mediators released by mast cells and other cells. These mediators all activate the HPA axis, resulting in high production of CRH, ACTH and cortisol via a series of intertwined mechanisms. At the same time, inflammation also makes cortisol less effective.  There are several ways for this to occur. Inflammation can cause cells to make fewer receptors for cortisol, meaning that no matter how much cortisol is made, only a small fraction will be able to act on cells.  Persistently high cortisol levels decrease production of other anti-inflammatory molecules and molecules that mediate the anti-inflammatory action of cortisol.  High cortisol also tells the HPA axis that it doesn’t need to make more cortisol, so even though more may actually be necessary, your body doesn’t know that.

All of these factors coalesce to form a reality where cortisol may be elevated but with little anti-inflammatory effect because of the changes I mentioned above. High cortisol is associated with mood symptoms.

Decrease of serotonin activity is also seen in mood disorders. Tryptophan is a precursor to serotonin, a hormone and neurotransmitter that heavily regulates mood.  Cortisol increases the activity of a molecule called tryptophan 2,3-dioxygenase (TDO), which removes the amino acid tryptophan from the pool of molecules to break down. Inflammatory molecules like interferon increase activity of the enzyme IDO, which decreases serotonin production.  IDO breaks down tryptophan to molecules that cannot be made into serotonin, such as kynerenin and quinolonic acid.  These metabolites have been observed as elevated in models of depression and anxiety.

Another way that inflammatory mediators affect the action of serotonin is to hasten its degradation. Both TNF and IL-6 increase the breakdown of serotonin to 5-HIAA.

References:

Furtado M, Katzman MA. Examining the role of neuroinflammation in major depression. Psychiatry Research 2015: 229, 27-36.

Rosenblat JD, et al. Inflamed moods: a review of the interactions between inflammation and mood disorders. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2014; 53, 23-34.

Interplay between mast cells and hormones: Part 1 of 8

Hormone Location released Major functions Interaction with mast cells Reference
Activin Ovaries Promotes FSH production and secretion 

Enhances activity of LH

 

Promotes wound healing

 

 Stimulates mast cell maturation 

Activin causes mast cells to increase expression of a gene (TAP) that in turn promotes more activin activity

 Funaba M, et al. Identified of tocopherol-associated protein as an activing/TGFb inducible gene in mast cells. Biochimica et Biophysica Acta – Molecular Cell Research 2006: 1768 (8), 900-906.
Adiponectin Adipose tissue, placenta Increase insulin sensitivity and transfer of glucose to cells from blood 

Protect against metabolic syndrome, diabetes mellitus and NASH

 

Suppress production of glucose

 Mast cells regulate formation of adipose tissue 

PGD2 drives differentiation of fibroblasts into adipocytes

 

Adiponectin may be associated with asthma in obese patients

 Nigro E, et al. Role of adiponectin in sphingosine-1-phosphate induced airway hyperresponsiveness and inflammation. Pharmacological Research 2016: 103, 114-122. 

Reena*, et al. Mast cell stabilizers obviate high fat diet-induced renal dysfunction in rats. European Journal of Pharmacology 2016: 777, 96-103.
Adrenocorticotropic hormone (ACTH)/ corticotropin Pituitary Stimulates corticosteroid and androgen synthesis and release in response to physical or emotional stress Binding at pituitary histamine H4 receptors induces release of ACTH 

Anaphylaxis and reactions trigger release of CRH, increasing release of ACTH

 Meng J, et al. Histamine H4 receptors regulate ACTH in AtT-20 cells. European Journal of Pharmacology 2008, 587: 335-336. 

Theoharides TC, et al. Mast cells and inflammation. Biochimica et Biophysica Acta 2012: 1822, 21-33.
Aldosterone and other mineralocorticoids Adrenal gland (cortex) Increases sodium and water reabsorption in kidney, increasing blood volume and blood pressure 

Promotes excretion of potassium and hydrogen ions from the kidney

 Aldosterone release is controlled by renin-angiotensin system 

Mast cell mediators such as chymase and renin participate in the renin-angiotensin system, driving up blood pressure.

 

Excessive release of serotonin by mast cells can also increase aldosterone production.

 Lalli E, et al. Local control of aldosterone production and primary aldosteronism. Trends in Endocrinology & Metabolism 2016: 27 (3): 123-131. 

Kennedy S, et al. Mast cells and vascular diseases. Pharmacology & Therapeutics 2013: 138, 53-65.
Amylin Pancreas Suppresses hunger reflex 

Slows gastric emptying

 Dysregulation of amylin contributes to lack of appetite and bloating in gastroparesis. 

Histamine binding at H1 receptor encourages release of amylin, causing appetite suppression.

 Potes CS, Lutz TA. Brainstem mechanisms of amylin-induced anorexia. Physiology & Behavior 2010: 100, 511-518. 

Kedar A, et al. Dysregulation of hormones insulin and amylin is associated with the symptoms of bloating and anorexia in diabetic gastroparesis. AGA Abstracts, Mo1583.
Angiotensin Liver Release of aldosterone 

Vasoconstriction

 

Increase of blood pressure

 Angiotensin participates in the angiotensin-renin system, which regulates blood pressure.Many mast cell mediators, such as chymase, carboxypeptidase  A and renin, participate in this system. Kolck UW, et al. Cardiovascular symptoms in patients with systemic mast cell activation disease. Translation Research 2016: x, 1-10. 

Kennedy S, et al. Mast cells and vascular diseases. Pharmacology & Therapeutics 2013: 138, 53-65.
Atrial natriuretic peptide (ANP) Heart Reduce systemic vascular resistance and water, sodium and fat in blood, decreasing blood pressure 

Decrease cardiac output

 

Vasodilator

 

 

 ANP directly activates mast cells, resulting in release of histamine, serotonin and TNF in a dose dependent fashion. 

ANP is associated with mast cell driven inflammation and swelling.

 Chai, OK. The role of mast cells in atrial natriuretic peptide-induced cutaneous inflammation. Regulatory Peptides 2011: 167, 79-85.

Mood disorders and inflammation: Mediators (Part 1 of 4)

Mood disorders are the leading cause of disability in many countries around the world. Depression alone affects a staggering number of people, currently thought to be about 350 million people worldwide.  Its prevalence and diagnosis is increasing to such an extent that the WHO expects it to be the primary cause of global disease burden in less than 15 years.

Mood disorders are commonly found in patients diagnosed with inflammatory conditions.  Cardiovascular disease, diabetes, metabolic syndrome, asthma, allergies and many autoimmune diseases co-occur with these psychiatric conditions.  While providers are often tempted to attribute depression, anxiety and maladaptive behaviors to the stress of having chronic health issues, a significant body of evidence firmly supports the idea that mood disorders are themselves inflammatory conditions and therefore biologically ordained. Furthermore, having a mood disorder can affect prognosis in some diseases.

A number of inflammatory molecules participate in immune response, including histamine, prostaglandins, bradykinin, leukotrienes, CRP, interferon, cortisol and cytokines.  These substances are released in response to physical stresses such as infection, trauma or disease process.  Psychological stress also triggers inflammatory response with increases of molecules such as IL-6, IL-1b, TNF and CRP.

Several studies have definitively found that mood symptoms are associated with increased levels of inflammatory markers.  PGE2, CRP, TNF, IL-1b, IL-2 and IL-6 were all elevated in both peripheral blood and cerebrospinal fluid in patients with major depressive disorder.  A massive 25-80% of hepatitis C patients experience depressive symptoms when they begin treatment with interferon, a potent inflammatory molecule. Elevated interferon and IL-2 levels have been observed early in the depressive event.

In human patients, studies have simulated an inflammatory response by inoculation with toxins, proteins associated with infectious organisms, or interferon. In one study, an inflammatory response was provoked by inoculation with Salmonella endotoxin.  While they suffered no physical symptoms, anxiety, depressed mood and decreased memory function was observed along with elevated TNF, IL-6 and cortisol levels.  Another study found that inoculation with LPS (a substance found in bacterial cell membranes) triggered a dose dependent increase in IL-6, IL-10, TNF, cortisol and norepinephrine, which in turn triggered a dose dependent increase in anxiety, “poor mind” and decreased long term memory functions.

References:

Furtado M, Katzman MA. Examining the role of neuroinflammation in major depression. Psychiatry Research 2015: 229, 27-36.

Rosenblat JD, et al. Inflamed moods: a review of the interactions between inflammation and mood disorders. Progress in Neuro-Psychopharmacology & Biological Psychiatry 2014; 53, 23-34.

 

Kounis Syndrome: Stress (Part 4 of 4)

The phenomenon we now called Kounis Syndrome has previously been called by names like morphologic cardiac reactions, acute carditis and lesions with basic characteristics of rheumatic carditis. It is sometimes still referred to as allergic angina or allergic myocardial infarction/heart attack depending upon the presentation. Allergic angina, which affected patients as microvascular angina, was first noted to progress to allergic heart attack in 1991.

In a small study done at a hospital, 31 patients with anaphylaxis or non-anaphylactic severe allergic reactions had higher serum troponin I than healthy control patients.  Among those 31 patients, those that experienced anaphylaxis had the highest troponin I overall.  This report, and similar findings, indicates that cardiovascular damage may be a frequent component of anaphylaxis, well beyond what is reported.

Mast cell patients often struggle to identify which is the chicken and which is the egg in the many instances of comorbid conditions. There is no such confusion here – mast cell activation causes Kounis Syndrome.  Tryptase increases in peripheral blood during a spontaneous heart attack.  However, when coronary spasm is induced with medications, there is no such increase in tryptase.  In instances where Kounis Syndrome was caused by disruption of an atherosclerotic plaque, mast cells entered the lesion and released mediators prior to the initiation of the coronary event.

Stress is well known to induce mast cell degranulation.  It has been documented in dozens of papers from various disciplines in the last twenty years. Corticotropin releasing hormone (CRH) is a stress hormone that can bind to the CRHR-1 receptor on mast cells, inducing the manufacture of VEGF. At the same time as CRH is released, neurotensin can also be released.  Experimental work has shown that stress induced mast cell degranulation can be compromised if the neurotensin receptor is blocked.

Reactive oxygen species can activate mast cells and induce sensory nerves to release substance P.  Substance P is a potent mast cell degranulator, inducing secretion of histamine and release of VEGF and other inflammatory mediators. These multiple activation pathways triggered by stress result in mast cell mediator release, which can induce coronary hypersensitivity syndromes such as Kounis Syndrome.

References:

Kounis NG, et al. Kounis Syndrome (allergic angina and allergic myocardial infarction). In: Angina Pectoris: Etiology, Pathogenesis and Treatment 2008.

Lippi G, et al. Cardiac troponin I is increased in patients admitted to the emergency department with severe allergic reactions. A case-control study. International Journal of Cardiology 2015, 194: 68-69.

Kounis NG, et al. The heart and coronary arteries as primary target in severe allergic reactions: Cardiac troponins and the Kounis hypersensitivity-associated acute coronary syndrome. International Journal of Cardiology 2015, 198: 83-84.

Fassio F, et al. Kounis syndrome: a concise review with focus on management. European Journal of Internal Medicine 2016; 30:7-10.

Kounis Syndrome: Aspects on pathophysiology and management. European Journal of Internal Medicine 2016.

Kounis NG. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management. Clin Chem Lab Med 2016

Kounis NG. Coronary hypersensitivity disorder: the Kounis Syndrome. Clinical Therapeutics 2013, 35 (5): 563-571.

Alevizos M, et al. Stress triggers coronary mast cells leading to cardiac events. Ann Allergy Asthma Immunol 2014; 112 (4): 309-315.

Kounis Syndrome: Treatment (Part 3 of 4)

Kounis Syndrome treatment requires amelioration of both allergic and cardiovascular symptoms.

  • Type I KS patients may only need treatment for allergic aspects without ever progressing to heart attack.
  • Type II and III KS patients are recommended to follow acute coronary event protocol recommended by ACS.
Treatment of allergic aspects of Kounis Syndrome
Drug class Medication Dosage Notes
H1 inverse agonist Diphenhydramine 1-2 mg/kg

50mg IV is a frequent dosage used for mast cell patients experiencing anaphylaxis symptoms

 Can cause hypotension and decrease blood flow through coronary artery if given bolus; should be given slowly
H2 antagonist Ranitidine 1 mg/kg
Famotidine 40mg IV is a frequent dosage used for mast cell patients experiencing anaphylaxis symptoms
Corticosteroid Methylprednisolone or other Methylprednisolone 120 mg IV is a frequent dosage used for mast cell patients experiencing anaphylaxis symptoms Corticosteroids are not used for immediate effect, but to prevent biphasic reactions.Corticosteroid treatment in active heart attack patients has not been found to be harmful.Corticosteroids were recommended as early as 2008 by Kounis for several reasons: inhibition of eicosanoid synthesis, decreasing amount of prostaglandins, leukotrienes and thromboxanes that can be made; reduction of inflammation by increasing death receptor CD95 on some cells; synthesis of annexins, proteins that modulate inflammatory cells and their actions

 

 
Fluid support IV fluids Crystalloid normal saline; avoid colloid solution Use with caution to avoid pulmonary edema
Epinephrine Epinephrine IM dose: 0.2-0.5mg every 5-15 minutes Can contribute to myocardial ischemiaCan prolong the QTc interval

Can cause coronary vasospasm and arrhythmias, especially if given IV

Glucagon is an alternative in patients for whom epinephrine is inappropriate

 

 

Treatment of coronary syndrome in Kounis Syndrome
Drug class Medication Dosage Notes
Nitroglycerin Nitroglycerin Sublingual: 0.3-0.4 mg every five minutesIV: 5-10mcg/min, increased by 10 mcg/min every 5 minutes Causes dilation of coronary vesselsIncreases bloodflow to counteract myocardial ischemia
Calcium channel blocker Diltiazem, verapamil Example  ER dosing for verapamil: 80mg orally every eight hours, immediate release Vasodilators
NSAID Aspirin 160-325 mg Prevent clot formation
P2Y12 receptor inhibitor Clopidogrel 75mg daily Taken with aspirin to prevent clot formation; some medical bodies recommend P2Y12 inhibitors with aspirin, while others recommend aspirin alone
Glycosaminoglycan Heparin IV: 5000 IU bolus, followed by infusion of heparin until PTT 1.5-2.5 above normal Type III patientsHeparin may cause allergic reaction, especially in bolus
Opioid Fentanyl 1-2 mcg/kg Drug of choice for pain management, causes small amount of mast cell degranulation, other opiates risk large scale degranulationDoes not affect cardiac output
N/A Stent placement if vessel narrowed by atherosclerosis N/A

 

Notes:

Beta blockers are contraindicated in Kounis Syndrome for the same reason they are contraindicated in mast cell patients – they block the action of epinephrine, which complicates treatment of anaphylaxis.

IV acetaminophen is generally well tolerated by mast cell patients but is not appropriate for Kounis Syndrome. Acetaminophen reduces cardiac output and systemic vascular resistance which can cause severe low blood pressure and aggravate cardiogenic shock.

References:

Kounis NG, et al. Kounis Syndrome (allergic angina and allergic myocardial infarction). In: Angina Pectoris: Etiology, Pathogenesis and Treatment 2008.

Lippi G, et al. Cardiac troponin I is increased in patients admitted to the emergency department with severe allergic reactions. A case-control study. International Journal of Cardiology 2015, 194: 68-69.

Kounis NG, et al. The heart and coronary arteries as primary target in severe allergic reactions: Cardiac troponins and the Kounis hypersensitivity-associated acute coronary syndrome. International Journal of Cardiology 2015, 198: 83-84.

Fassio F, et al. Kounis syndrome: a concise review with focus on management. European Journal of Internal Medicine 2016; 30:7-10.

Kounis Syndrome: Aspects on pathophysiology and management. European Journal of Internal Medicine 2016.

Kounis NG. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management. Clin Chem Lab Med 2016

Kounis NG. Coronary hypersensitivity disorder: the Kounis Syndrome. Clinical Therapeutics 2013, 35 (5): 563-571.

Kounis Syndrome: Diagnosis (Part 2 of 4)

Separating the symptoms of the coronary syndrome from those caused by the coincident allergic reaction is difficult.  Acute chest pain is the hallmark symptom of Kounis Syndrome. While other symptoms may be present, such as nausea, fainting, and shortness of breath, they can also be attributed to the allergic reaction.  Likewise, many of the clinical markers for KS may also appear during anaphylaxis, including cold extremities, very fast or very low heart rate, low blood pressure, palpitations, and sweating. Given the significant overlap in presentation with allergic symptoms, KS is not often diagnosed, though it likely affects a larger population than represented in literature.

Troponins and cardiac enzymes like creatinine kinase are important markers for coronary syndrome, but they are not always elevated in KS. Measurement of mast cell mediators like histamine or tryptase is not always accurate due to the short lifetime of these molecules in the body.  Released histamine is only present in blood for about eight minutes, while tryptase has a half-life of about ninety minutes.

An electrocardiogram (EKG) should be performed as part of the diagnostic process.  A number of signs have been seen in KS patients, including atrial or ventricular fibrillation, bigeminal rhythm, heart block, nodal rhythm, sinus bradycardia or tachycardia, ST segment depression or elevation, T-wave flattening or inversion, QRS or QT prolongation, and ventricular ectopics.  Beyond EKG, there are additional markers that may be present with Kounis Syndrome.  A chest x-ray may show an enlarged heart.  Echocardiogram may show dilated cardiac chambers. Angiography of the coronary artery can reveal spasm or thrombosis. In coronary biopsies, infiltration by mast cells and eosinophils may be found.  Elevation of eosinophils in the blood may also be present.

Having no history of coronary artery disease can make diagnosis more complicated for KS Type I patients, who also may have normal troponins and EKG. Dynamic cardiac MRI with gadolinium can show a subendocardial lesion in patients with KS Type I. Newer imaging techniques such as SPECT have been able to identify myocardial ischemia in KS Type I where coronary angiography had showed no irregularities.

References:

Kounis NG, et al. Kounis Syndrome (allergic angina and allergic myocardial infarction). In: Angina Pectoris: Etiology, Pathogenesis and Treatment 2008.

Lippi G, et al. Cardiac troponin I is increased in patients admitted to the emergency department with severe allergic reactions. A case-control study. International Journal of Cardiology 2015, 194: 68-69.

Kounis NG, et al. The heart and coronary arteries as primary target in severe allergic reactions: Cardiac troponins and the Kounis hypersensitivity-associated acute coronary syndrome. International Journal of Cardiology 2015, 198: 83-84.

Fassio F, et al. Kounis syndrome: a concise review with focus on management. European Journal of Internal Medicine 2016; 30:7-10.

Kounis Syndrome: Aspects on pathophysiology and management. European Journal of Internal Medicine 2016.

Kounis NG. Kounis syndrome: an update on epidemiology, pathogenesis, diagnosis and therapeutic management. Clin Chem Lab Med 2016

Kounis NG. Coronary hypersensitivity disorder: the Kounis Syndrome. Clinical Therapeutics 2013, 35 (5): 563-571.

Kounis Syndrome: Subtypes and effects of mast cell mediators (Part 1 of 4)

Kounis Syndrome (KS) is an acute coronary syndrome that arises as a direct result of mast cell degranulation during an allergic or anaphylactic reaction.

KS usually presents as chest pain during an acute allergic or anaphylactic reaction. There are three recognized variants:

Type I: Patient has no predisposing coronary artery disease.

There are two possible outcomes:

  • Coronary artery spasm with no appreciable increase in cardiac enzymes or troponins
  • Coronary artery spasm that evolves to acute myocardiac infarction (heart attack) with accompanying increase in cardiac enzymes or troponins

Type II: Patient has history of coronary artery disease. There are two possible outcomes:

  • Coronary artery spasm with no appreciable increase in cardiac enzymes or troponins
  • Plaque erosion or rupture that evolves to acute myocardiac infarction (heart attack) with accompanying increase in cardiac enzymes or troponins

Type III: Patient has history of coronary artery disease and a drug eluting coronary stent. There are two possible outcomes:

  • Coronary artery spasm with no appreciable increase in cardiac enzymes or troponins
  • Thrombosis that evolves to acute myocardiac infarction (heart attack) with accompanying increase in cardiac enzymes or troponins

A number of mast cell mediators have effects that can cause coronary spasm or thrombosis.  Beyond their direct effects, they also perpetuate an inflammatory cycle that results in activation and infiltration by inflammatory cells

Mediator Effect
Histamine Coronary vasoconstriction, activation of platelets, increase expression of tissue factor
Chymase Activation of interstitial collagenase, gelatinase, stromelysin resulting in plaque rupture, generation of angiotensin II, a powerful vasoconstrictor
Cathepsin D Generation of angiotensin II, a powerful vasoconstrictor
Leukotrienes (LTC4, LTD4, LTE4) Powerful vasoconstrictor, levels increased during acute unstable angina
Tryptase Activation of interstitial collagenase, gelatinase, stromelysin resulting in plaque rupture
Thromboxane Platelet aggregation, vasoconstriction
PAF Vasoconstriction, aggregation of platelets
Platelets Vasoconstriction, thrombosis

 

References:

Kounis Syndrome (allergic angina and allergic myocardial infarction). Kounis NG, et al. In: Angina Pectoris: Etiology, Pathogenesis and Treatment 2008.

Lippi G, et al. Cardiac troponin I is increased in patients admitted to the emergency department with severe allergic reactions. A case-control study. International Journal of Cardiology 2015, 194: 68-69.

Kounis NG, et al. The heart and coronary arteries as primary target in severe allergic reactions: Cardiac troponins and the Kounis hypersensitivity-associated acute coronary syndrome. International Journal of Cardiology 2015, 198: 83-84.

Fassio F, et al. Kounis syndrome: a concise review with focus on management. European Journal of Internal Medicine 2016; 30:7-10.

Kounis Syndrome: Aspects on pathophysiology and management. European Journal of Internal Medicine 2016.

Motion carries

For questions that have generic answers, I will remove identifying information and then answer them in a post.  For questions that involve consideration of significant history, I will respond privately in email as soon as I am able.  These posts will be marked “Q&A” and will be indexed in a dropdown menu.

I am taking a break this week from MastAttack (site, FB and email) to relax and get some rest.  I have set up auto posts for this week, including a series on Kounis Syndrome that discusses pathology, diagnosis and treatment.

Hope everyone has a great week!

xoxo

Lisa

Symptoms, mediators and mechanisms: A general review (Part 2 of 2)

 

Gynecologic symptoms    
Symptom Mediators Mechanism
Irregular and painful menstruation Histamine (H1), bradykinin Smooth muscle constriction
Uterine contractions Histamine (H1), serotonin, bradykinin Smooth muscle constriction

Increased estrogen

 

 

Neurologic symptoms    
Symptom Mediators Mechanism
Appetite dysregulation Histamine (H1), histamine (H3), leptin Dysfunctional release of neurotransmitters, suppression of ghrelin
Disorder of movements Histamine (H2), histamine (H3) Dysfunctional release of neurotransmitters, increases excitability of cholinergic neurons
Memory loss Histamine (H1), histamine (H3) Dysfunctional release of neurotransmitters
Headache Histamine (H1), histamine (H3), serotonin (low) Dysfunctional release of neurotransmitters

 

Low serotonin

 

Decreased blood flow to brain
Depression Serotonin (low), TNF, histamine (H1) Low serotonin

Disordered release of dopamine
Irregular sleep/wake cycle Histamine (H1), histamine (H3), PGD2 Dysfunctional release of neurotransmitters
Brain fog Histamine (H3), inflammatory cytokines Dysfunctional release of neurotransmitters, neuroinflammation
Temperature dysregulation Histamine (H3) Dysfunctional release of neurotransmitters, dysfunctional release of catecholamines

 

 

Miscellaneous symptoms    
Symptom Mediators Mechanism
Bleeding diathesis (tendency to bleed easily) Tryptase, heparin Participation in anticoagulation pathways

In which I am so hopelessly behind

Hi, everyone –

I am weeks behind in responding to some emails and comments.  I don’t want anyone to think I’m ignoring them.

I am strongly considering stripping some questions of identifying information and posting the responses on a weekly basis because I am often asked similar nuanced questions that aren’t really completely addressed in any one post I have already written.  What do you guys think?  Does anyone strongly object to this?  I would ensure that the question would not be identifying.

Thanks for your patience!

Lisa