Platelet Disorders

Platelet Disorders

von Willebrand’s disease

* the most common inherited coagulopathy caused by a defect in von Willebrand factor, which aids the binding of platelets to collagen
* chromosome 12, autosomal dominant
* Bleeding related to platelets (epistaxis, gingival, gums) with a normal platelet count;
* exacerbated by the use of aspirin
* it is a protective carrier for factor VIII; hence factor VIII may be low and hence aPTT may be elevated (50%)

Dx –

* low vWF (antigen) level;
* Ristocetin cofactor assay (or vWF activity) – detects vWF dysfunction; deficient ristocetin-induced platelet aggregation
* it means there is no response to ristocetin but this is corrected with the addition of normal plasma

* low factor VIIIc;
* prolonged BT

Scenario:
The combination of a petechial skin rash combined with a slightly elevated APTT and reduced factor VIII activity make Von Willebrand’s disease the most likely diagnosis, though hemophilia will be given in the answer choices

Tx –
DDAVP (desmopressin) if mild, and with vWF concentrate


Bernard-Soulier syndrome

  • autosomal recessive
  • disease of platelet adhesion which causes prolonged bleeding times in the presence of normal platelet counts.
  • These defective platelets cannot bind to subendothelial collagen properly because of a deficiency or dysfunction of the glycoprotein Ib-IX complex.
  • Dx
    • Clinically the patients have impaired hemeostasis and recurrent severe mucosal hemorrhage.
    • bleeding out of proportion to the degree of thrombocytopenia
    • mild thrombocytopenia, circulating “giant” platelets, severe platelet dysfunction; Hb may be low because of blood loss
    • platelets do not aggregate in response to ristocetin, but have a nornal aggregation in response to adenosine diphosphate (ADP), epinephrine and collagen
  • Tx
    • The only treatment for an acute episode is a transfusion of normal platelets.
    • Cryoprecipitate or vWF concentrate do not help

May–Hegglin anomaly (MHA)

  • May–Hegglin anomaly (MHA), also known as Dohle leukocyte inclusions with giant platelets and macrothrombocytopenia with leukocyte inclusions
  • autosomal dominant, MYH9 gene defect (22q12-13)
  • may found in association with Alport Syndrome
  • So, look for high frequency hearing loss (82%), proteinuria (40%), cataracts (25%), Hematuria (25%)

Glanzmann’s Thrombasthenia

autosomal recessive

platelet glycoprotein IIb/IIIa complex is either deficient or present but dysfunctional leading to defective platelet aggregation and subsequent bleeding

Dx

  • Platelet counts and other coagulation tests (PT, PTT) are normal
  • Prolonged BT
  • Primary platelet aggregation response to platelet agonists such as adenosine diphosphate, epinephrine, and collagen is decreased, while the response to ristocetin is normal

Tx

  • platelet transfusion in case of active bleeding

 

May-Hegglin anomaly is rare and not really tested in questions. Also, it is in fact primarily a morphology and quantitative platelet disorder but I put it as a side note to compare.

My way to remember:

  1. May-Hegglin is Dominant because of Dohle and Giant platelets; remember also Alport is (x-lined) dominant
  2. Bernard-Soulier has 2 names ADHERED (adhesion problem); so it becomes Giant and do not listen to Ristocetin
  3. Glanzmann has “G” for AGGreGation and aGree to ristocetin while response to others are decreased

 

 

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Diarrhea and Gastroenteritis

Diarrhea and Gastroenteritis

Definition:

Consistency is much more important than frequency to define diarrhea…

Types

Watery, osmotic (e.g, Laxative-induced diarrhea),

secretory (eg, microscopic colitis)

Functional – mucus (typically from irritable bowel syndrome)

Inflammatory – blood +/- pus (eg, IBD as in Chron’s and UC, some invasive bacteria)

Fat (steatorrhea)

Case Approach:

Two main questions to answer are:
  1. Acute or Chronic
  2. Watery (non-bloody) or Bloody

Blood and WBCs in stool

Salmonella: contaminated poultry and eggs; more common in patients with SCD and achlorhydria
 
Campylobacter jejuni: most common cause, rarely associated with GBS
 
E. coli  O157:H7 — undercooked hamburger meat; hemolytic uremic syndrome (HUS)
 
Shigella: 2nd most common association with HUS
 
Vibrio parahaemolyticus: shellfish and cruise ships
Vibrio vulnificus: raw shellfish, h/o liver disease, iron overload and bullous skin lesions
                          * may cause invasive, life-theratening disease in immunocompromised patients or those with liver disease
 
Yersinia enterocolitica: high affinity for iron, hemochromatosis, blood transfusions; can mimic appendicitis or Chron’s disease
               tends to infect the cecum rather than distal colon
 
Clostridium difficile:  previous antibiotic use;  white and red cells in stool
Clostridium botulinum :   infected canned foods
Clostridium perfringens:  meats taht have been contaminated with spores by being unrefrigerated
 The major protozoan associated with blood in the stool is Entamoeba histolytica.

No Blood and WBCs in stool

  • Viral
  • Giardia lamblia
  • Cryptosporidiosis/ isospora: AIDS with CD4 <50-100; detected by modified acid fast stain (treat underlying AIDS, nitazoxanide which is superior to paromomycin)
  • Bacillus cereus: vomiting –  warmed or slowly re-heated fried rice
  • Staphylococcus: vomiting
Dx
  • The best initial test is for  blood and/or fecal leukocytes with methylene blue testing
  • Stool lactoferrin has greater sensitivity and specificity compared with stool leukocytes
  • The most accurate test = stool culture to determine the specific type
  • Modified acid-fast test for cryptosporidiosis because routine fecal O/P does not reliably pick up
  • ELISA stool antigen test for Giardiasis (90% sensitivity); 3 fecal O/P for Giadria has lesser sensitivity (80%) than single stool antigen test
Tx
  • supportive
  • consider antibiotics only when abdominal pain, blood in the stool, and fever
  • best initial empirical = ciprofloxacin or other fluoroquinolones +/- metronidazole
  • TMP/SMX for Isopora
  • Doxycycline for Vibrio vulnificus
  • Rifaximin for traveler’s diarrhea

Giardia lamblia

  • flagellated protozoan, often acquired during hiking/ camping activities, by drinking unpurified water from streams
  • affects small bowel (duodenum and proximal jejunum) producing upper GI symptoms such as frequent burping, bloating, distention, flatus, and loose, nonbloody, foul-smelling and fatty diarrhea (steathorrhea).
Dx:
  • duodenal aspirate/ biopsy/ immunoassay
  • stool for parasites/ eggs
  • stool ELISA
Tx-
  •   metronidazole/ Tinidazole
**Giardiasis is the only common primary infection causing chronic malabsorption.

Pseudomembranous colitis

caused by C. difficile; Gram +ve superbug whose spores are contagious (fecal-oral or from the environment)
Girotra’s triad
  1. Increasing abdominal pain/distention and diarrhea
  2. Leukocytosis > 18,000
  3. Hemodynamic instability
Tx
  • Stop the causative antibiotic (if possible)
  • No treatment if asymptomatic
  • Metronidazole for symptomatic cases
  • Vancomycin may be better in severe disease
  • Consider surgery (urgent colectomy) if complications such as toxic megacolon developed; raised LDH and in deteriorating patient

Initial evaluation of Chronic diarrhea

Fat:
  • most useful screening test is stool for fat (Sudan red stain)
  • confirm with 72-hour stool for fecal fat (gold standard for steatorrhea)
  • Steatorrhea is most prominent with pancreatic insufficiency; all require a sweat chloride (to rule out CF and Schwachman-Diamond $)
  • Serum trypsinogen may also be used
  • Screen for carbohydrate malabsorption — measure reducing substances in stool (Clinitest)
  • Breath hydrogen test
  • Protein loss — difficult to evaluate directly
  • Screen with spot stool alpha-1 anti-trypsin level

Differential Diagnoses of Chronic Diarrhea

  1. most common infectious cause = Giadiasis
  2. most common congenital cause with malabsorption = cystic fibrosis
  3. most common anomaly cause with incomplete bowel obstruction + malabsorption= malrotation

Polycythemia

Polycythemia

Primary polycythemia/ Polycythemia vera

  • a.k.a polycythemia rubra vera; erythremia
  • common in age 60 – 75
  • overproduction of all three hematopoietic cell lines with predominant elevation in red cell counts
  • mutation in the JAK2 protein which regulates marrow production
  • red cells grow wildly despite a Low erythropoietin level
  • high serum leukocyte alkaline phosphate
features:
  • Headache, blurred vision, and tinnitus
  • pruritus, especially after hot bath (due to histamine release from increased numbers of basophils)
  • HTN, facial plethora, fatigue, Splenomegaly
  • Bleeding from engorged blood vessels
  • Thrombosis from hyperviscosity
Investigation,
  • elevated Hct >60%*
  • low MCV and Low iron (because of excessive usage and production)
  • however, Vit. B12 levels are elevated for unclear reason
  • exclude hypoxia first; normal Oxygen level and *low erythropoietin level in PV
* RCC also has elevated Hct, but the erythropoietin is elevated.
* A small number of patients can convert to AML.
Tx
  • initial 1st line – Phlebotomy and aspirin prevent thrombosis – target Hct 45%
  • Hydroxyurea helps lower the cell count
    • indicated in old age >70 years; has thrombosis; has a platelet count >1500; and has cardiovascular risk factors
  • Allopurinol or rasburicase protects against uric acid rise
  • Antihistamines
  • Interferon alpha may be used in refractory cases
Platelet counts elevate temporarily after spleen removal

Secondary polycythemia
Increased erythropoietin level
2° to chronic tissue hypoxia
 

Kidney cancer is an important differential diagnosis of secondary polycythemia.

Renal Cell Carcinoma is a neoplastic condition that can initially appear with many different paraneoplastic manifestations.

The initial presentation may include hypertension, flank mass, gross or microscopic hematuria, hypercalcemia, fever, weight loss, and/or polycythemia.

Polycythemia may be the presenting sign in 3% of cases of kidney cancer.

Careful evaluation is important in patients presenting with polycythemia and hematuria.

Polycythemia is secondary to a hypersecretion of tumor cytokines, including renin.

The patient’s erythropoietin level is usually high.

Surgical removal of the cancer resolves the polycythemia.

Poisoning with Alcohol and Related Substances

Poisoning with Alcohol and Related Substances

Methanol and Ethylene glycol poisoning

1) Methanol can cause retina injury leading to blindness ( eye manifestations can happen as early as 15-20 hours post ingestion) ?  secondary to the accumulation of formic acid/ formaldehyde;

That’s why the first thing you do in suspected methanol poisoning is …

to check retinal inflammation

Methanol can be found in wood solvent, sterno, paint thinner, photocopier fluid, and cleaning solutions such as windshield washer solution

2) Ethylene glycol (coolant, anti-freeze) poisoning
toxic metabolite is Oxalic acid/ oxalate >> damage kidneys
usually has 3 distinct clinical phases-

  1. first stage- CNS effects ( first 12 hours),
  2. second stage- cardiopulmonary effects ( HTN, CCF, ARDS etc) metabolic acidosis with high anion gap and high osmolar gap and
  3. third stage- renal effects- ARF.

Tip to memorize: You see? going from top to bottom in order –  CNS -> CVS -> Renal

Initial Dx – check hypocalcemia, envelope-shaped oxalate crystals in urine

Mx

Acute management include gastric lavage and correct the metabolic acidosis.
fomepizole, an inhibitor of alcohol dehydrogenase, is now used first-line in preference to ethanol, however it cannot remove toxic substance formed already.


Haemodialysis can be done for effective and faster removal of the toxic metabolites.

Folinic acid can be used to protect against ocular toxicity of methanol whereas thiamine are administered to drive metabolism of ethlylene glycol to non-toxic metabolism.

Isopropyl alcohol ingestion and toxicity may be known only by the history, presentation with normal anion gap acidosis and specific drug level.

Alcohol

Mild withdrawal:
  • tremors, tachycardia, and anxiety;
  • Seizures may occur 6-12 hrs after the last drink
Delirium tremens (DT):
  • manifests 48-72 hrs after the last drink but can last up to 10 days
  • Mental confusion
  • autonomic hyperactivity
  • visual hallucinations
  • severe agitation
  • diaphoresis
Alcoholic hallucinosis:
  • may be confused with DT
  • starts 12-24 hours after last drink but can last days to weeks
  • Paranoid psychosis without tremors and confusion
  • Normal vital signs (no HTN and tachycardia)
  • No agitation
  • Normal appearance except for auditory (most common), visual, or tactile hallucinations
Wernicke encephalopathy:
  • Confusion, ataxia, and ophthalmoplegia (nystagmus)
Korsakoff psychosis:
  • Amnesia and confabulations
*alcohol withdrawal has a very high mortality rate (5%)
Tx
Benzodiazepines
avoid antipsychotics/neuroleptics such as haloperidol (due to risk of lower seizure threshould and prolonged QT interval)

Food Poisoning from Fish/Seafood

Food Poisoning from Fish/Seafood
Scombroid food poisoning
results from eating spoiled (decayed) fish — most commonly reported with mackerel, tuna , bluefish, mahi-mahi , bonito, sardines , anchovies , and related species of fish that were inadequately refrigerated or preserved after being caught.
most rapid onset; allergic symptoms — wheezing, flushing, rash; in severe cases – resp distress, blurred vision, tongue swelling
Tx: antihistamines (eg, DPH)
 
Ciguatera
is the most common nonbacterial foodborne illness caused by eating certain reef fish whose flesh is contaminated with toxins originally produced by dinoflagellates such as Gambierdiscus toxicus which live in tropical and subtropical waters.
Most commonly implicated fish are barracuda, red snapper, and grouper
Onset within 2-6 hours;
S/S – Neurological symptoms – paresthesias, numbness, weakness, reversal of heat and cold as well as nausea, vomiting, and abdominal cramps
Saxitoxin is the toxin found in shellfish that ingest particular dinoflagellates
The toxin affects neuronal transmission leading to symptoms of cranial nerve dysfunction and muscle weakness — high risk for respiratory failure
Tetrodotoxin is the toxin expressed by the puffer fish, a fish considered to be a delicacy in some eastern Asian countries
S/S-  perioral numbness, increasing neurologic dysfunction, and eventual respiratory arrest secondary to profound muscle weakness

Myanmar’s Worst Ever Flood Disaster

‪#‎save_myanmar‬

Myanmar (or Burma) has been suffering from the recent flood disaster. This flood can be regarded as one of the worst disasters in decades. Most of the cities in 10 out of 14 States (or Divisions) are already under water now. Reportedly, up to 150,000 people had been displaced or had their livelihoods affected due to this terrible flood. More torrential rain is expected in the coming days according to weather forecast. This status has been posted in order to create the awareness for this flood disaster in Myanmar and let all countries across the world know that flood victims are in need of help for their survival and rehabilitation. Moreover, people in disaster zones are dying everyday due to lack of food, clean water and basic necessities for life. For people in Burma, you can check this websitehttp://www.myanmarflood.info/ for more information and donation. And also please copy and paste this status on your timeline along with hash-tags below to create international awareness. Your help is one of the necessities for flood victims.

‪#‎SaveMyanmar‬ ‪#‎SaveBurma‬ ‪#‎SupprotMyanmar‬ ‪#‎SupportBurma‬
Myanmar Flood Data
myanmarflood.info ·
I start to do a donations for Water Flood in Myanmar. I need a help & Supports of all of my fris, bros & siss. Plz donate & help the peoples who are in trouble. 😞😞😞

私は、ミャンマーにおける水洪水のための寄付を行うことを開始します。私は私の友人、兄弟&姉妹のすべての助けと支援を必要とします。寄付&困っている人々を助けてください。

나는 미얀마 물 홍수에 대한 기부금을 시작합니다. 나는 나의 친구, 형제 및 자매 모두의 도움말 및 지원하는 필요합니다. 기부 및 문제가있는 사람들을 도와주세요.

我开始做一个捐赠淹缅甸。我需要帮助,我所有的朋友,兄弟姐妹的及支援。请捐款帮助与谁是麻烦的人民。

ฉันจะเริ่มต้นที่จะทำสำหรับการบริจาคน้ำท่วมน้ำในพม่า ฉันต้องการความช่วยเหลือและรองรับทั้งหมดของเพื่อน ๆ พี่ ๆ น้อง ๆ และน้องสาว กรุณาบริจาคและช่วยให้คนที่กำลังมีปัญหา

Ben Myanmar Su Flood için bağış yapmaya başlar. Ben arkadaşlarım, kardeşler ve sisterss tüm bir yardım ve Destekler gerekir. Bağış ve başı dertte olan halklara yardım edin.

Sisimulan ko na gawin ang isang donasyon para sa Water Flood sa Myanmar. Kailangan ko ng tulong & sumusuporta sa lahat ng aking mga kaibigan, mga kapatid at kapatid na babae. Mangyaring mag-abuloy at matulungan ang mga mamamayan na nagkakaproblema.

मैं म्यांमार में पानी बाढ़ के लिए एक दान करना शुरू करते हैं। मैं अपने दोस्तों, भाइयों और बहनों के सभी की एक मदद और समर्थन करता है की जरूरत है। दान और मुसीबत में हैं, जो लोगों की मदद करें।

ຂ້າພະເຈົ້າເລີ່ມຕົ້ນເພື່ອເຮັດການບໍລິຈາກສໍາລັບນ້ໍາ້ໍາຖ້ວມໃນມຽນມາໄດ້. ຂ້າພະເຈົ້າຕ້ອງການການຊ່ວຍເຫຼືອແລະການສະຫນັບສະຫນູນຂອງທັງຫມົດຂອງຫມູ່ເພື່ອນອ້າຍນ້ອງຂອງຂ້າພະເຈົ້າ, ແລະເອື້ອຍນ້ອງ. ກະລຸນາບໍລິຈາກແລະການຊ່ວຍເຫຼືອປະຊາຊົນຜູ້ທີ່ມີບັນຫາໃນການ.

Eu começo a fazer doações para uma inundação de água em Myanmar. Eu preciso de uma ajuda e Suporte de todos os meus amigos, irmãos e sisterss. Por favor, doe e ajudar os povos que estão com problemas.

Ich fange an, eine Spende für Wasser Überschwemmung in Myanmar zu tun. Ich brauche eine Hilfe & Supports aller meiner Freunde, Brüder und sisterss. Bitte spenden Sie und um die Völker, die in Schwierigkeiten sind.

Αρχίζω να κάνει μια δωρεά για το Νερό πλημμύρες στη Μιανμάρ. Χρειάζομαι βοήθεια & Βάσεις όλους τους φίλους μου, τους αδελφούς και sisterss. Παρακαλούμε να δωρίσουν και να βοηθήσει τους λαούς που βρίσκονται σε δύσκολη θέση.

Я начинаю делать пожертвования для воды Потопа в Мьянме. Я нужна помощь & Опоры всех моих друзей, братьев и sisterss. Пожалуйста, поддержите и помочь народам, которые попали в беду.

AP Htwe's photo.
AP Htwe's photo.
AP Htwe's photo.

Paracetamol Poisoning

Toxic dose = 150mg/kg (75mg/kg if malnourished) or 12g in adults may be fatal (10-15g ~ 20-30 tablets)
Max. Therapeutic dose = 4g/day

Acute poisoning:
1 hr = larvage + activated Charcoal
4 hr = Paracetamol level
8 hr = N-acetylcysteine (within 8 hr, effectiveness is the same, afterwards it declines); alternative – Methionine
12 hrs = Review and repeat INR q12h
24 hr = review with results (see criteria for transfer)
48 h = review (if INR normal and pt stable, possible home)

N-acetylcysteine

  • to replenish hepatic glutathione

IVI regieme

1. 150mg/kg in 200mL of 5%DW x 15min
2. 50mg/kg in 500mL of 5%DW x 4 hr
3. 100mg/kg in 1L of 5%DW x 16 hr

 

Crieteria for transfer

  • Encephalopathy or increased ICP
  • INR >2.0 at <48 hr – or >3.5 at <72h (peak at 72-96h) N.B. LFTs are NOT good markers
  • Renal impairment ( Creat > 200), consider HD if >400) * monitor urine output and daily U&Es
  • Acidosis / Blood pH <7.3
    • Lactate > 3.5 mg/dL (0.39 mmol/L) 4 hrs after early fluid resuscitation
    • Lactate > 3 mg/dL (0.33 mmol/L) after full fluid resuscitation at 12 hours
  • Systolic BP < 80mmHg

 

King’s College Hospital Criteria for Liver transplantation

Paracetamol liver failure

  • Arterial pH <7.3 24 h after ingestion

Or all of the following:

  • PT > 100s
  • Creat > 300
  • Grade III or IV encephalopathy

Non-paracetamol liver failure

  • PT > 100s

Or 3 out of 5 of the following:

  1. Drug-induced liver failure
  2. Age <10 or >40y old
  3. >1wk from 1st Jaundice to encephalopathy
  4. PT > 50s
  5. Bilirubin > 300