Miscellaneous Flashcards
Lab features of factor XI deficiency and diagnosis
- Prolonged aPTT, which corrects with mixing study
- confirmation by factor XI activity
Factor XI clinical features
- Bleeding phenotype highly variable
- NO spontaneous bleeding, hemarthrosis, or muslce hematomas
- Bleeding typically in setting of trauma or surgery - “injury-related bleeding disorder”
Factor XI deficiency management
- if significant bleeding history, factor XI replacement
- IF significant bleeding and inhibitor present, recombinant factor VIIa
PCH diagnosis
clinical/laboratory
- clinical context of hemolysis precipitated by the cold
- Coombs/DAT + complement (C3) (but can be negative in kids), negative for IgG or IgM
- ideally Donath-landsteiner antibody (But insensitive and can rapidly become negative)
Deauville X meaning
New areas of uptake unlikely to be related to lymphoma
Deauville 5 meaning
Uptake markedly higher than liver (2-3x) and/or new lesions
Deauville 4 meaning
Uptake moderately more than liver uptake, at any site
Deauville 3 meaning
Uptake greater than mediastinal blood pool but less than liver
Deauville 1 meaning
No uptake
Deauville 2 meaning
Uptake less than mediastinal blood pool
Morphine IV to PO conversion
1 mg IV = 3 mg PO
Niraparib dosing based on weight and plt count
Patients <77 kg or with a platelet count <150,000/mm3: Oral: 200 mg once daily
Patients ≥77 kg and with a platelet count ≥150,000/mm3: Oral: 300 mg once daily
Cryoprecipitate components
- Fibrinogen
- Factor XIII
- Von willebrand factor
- Fibronectin
VITT presentation
*Strongly mimics HIT
1) vaccine type – J&J, Astra Zeneca
2) timeframe – typically in a narrow window 5 to 10 days post-vaccination, leading to identification of cases typically between 5 to 30 days post-vaccination (so 5-30 currently used as interval)
3) thrombosis – (most commonly in cerebral veins (including intracranial hemorrhage), deep veins of the leg, pulmonary arteries, and splanchnic vessels). Both arterial + venous.
*But can have thrombosis without thrombocytopenia or thrombocytopenia without thrombosis.
4) Platelet count nadir – between 10,000 and 100,000/microL, with a median platelet count of 47k
5) High frequency of DIC.
VITT diagnosis
Positive PF4 antibody + appropriate clinical context (post-COVID vaccine thrombosis and/or thrombocytopenia)
VITT management
- ***High dose IVIG 1 gm/kg (based on actual body weight) daily for 2 days (reduce VITT antibody-induced platelet activation)
- anticoagulation (DOAC preferred)
Duration of anticoagulation for VITT
IF thrombosis → Anticoagulation for minimum 3 months after normalization of the platelet count, as long as no further thrombosis occurs
IF NO thrombosis –> anticoagulation until platelet count recovery and perhaps longer if tolerated (four to six weeks after platelet count recovery)
Porphyria mechanism generally
- Porphyrias are caused by alterations in the enzymes of heme biosynthesis. Heme is essential in the function of many hemoproteins, including hemoglobin and hepatic cytochrome P450 enzymes.
Treatment for AIP
hemin
1) Diagnosis of AIP 2) confirmatory testing specific for AIP
1) elevated plasma and urinary ALA and PGB above baseline (>10 mg/L or >10mg/g)
2) normal or slightly elevated total plasma porphyrins
3) normal or slightly increased stool porphyrins
Confirmatory testing:
1) ***low erythrocyte PBGD activity (deficient enzyme in AIP)
2) genetic testing
AIP clinical features
- develop over hours to days + insomnia as early symptom + persist for days to weeks + unexplained acute abdominal pain (85-95%, poorly localized) + unexplained psychiatric symptoms + peripheral neuropathy + vomiting + muscle weakness + pain in limbs/head/neck/chest + bladder dysfunction + dark or reddish-brown urine
AIP pathophysiology
Inherited deficiency of porphobilinogen deaminase (PBGD; also called hydroxymethylbilane synthase [HMBS]), the third enzyme in the heme biosynthetic pathway
Chronic granulomatous disease diagnosis
- undergo neutrophil-function testing (cytochrome c reduction assay, chemiluminescence, nitroblue tetrazolium (NBT) reduction test, and dihydrorhodamine (DHR) 123 oxidation test (preferred))
- Positive findings should be confirmed by genotyping
CGD clinical features
- recurrent, life-threatening bacterial and fungal infections + granuloma formation
CGD mechanism
defects in the phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex
MBL diagnostic criteria
1) monoclonal B cell population (flow cytometry preferred)
2) <5000 cells/microL
3) >3 months
4) no other features of a b cell lymphoproliferative disorder (lymphadenopathy, organomegaly, cytopenias, or extramedullary involvement) or autoimmune disorder or infectious disease
X-linked sideroblastic anemia (XLSA) clinical features
- young boy presenting with hgb of 7 with microcytosis and no evidence of iron deficiency
XLSA treatment
B6
1) 2 categories of sideroblastic anemias 2) causes in second category
1) clonal sideroblastic anemias, which are stem cell disorders (MDS, MPN)
2) sideroblastic anemia attributed to copper deficiency, certain medications, or excessive alcohol use
Settings in which copper deficiency develops
1) malabsorption
2) prolonged parenteral nutrition
3) zinc ingestion
Work up for ring sideroblast detected on bone marrow aspirate
Review for history of excessive alcohol use
Test for copper deficiency
Review medications for drug-induced sideroblastic anemia
IF above nondiagnostic, genetic testing: ALAS2 (female only), SF3B1 and JAK2
Primary complication of sideroblastic anemia to be aware of
- iron overload (ineffective erythropoiesis leads to increased iron absorption)
What is Heyde syndrome?
VWF is thought to suppress angiogenesis. Patients with aortic stenosis or severe MR have been found to have increased GI angiodysplasia (Heyde syndrome) thought secondary to acquired VWS and VWF deficiency
Brodifacoum is
superwarfarin, used as rodenticide, common cause of toxic ingestion leading to coagulopathy
1) Management of toxic ingestion of anticoagulant rodenticides 2) management of associated severe bleeding
- Activated charcoal (assuming normal mental status and no aspiration risk and can be given within 2 hrs)
- IF normal coags 48h after ingestion, no treatment
- IF INR less than 4.5 and no bleeding, monitor
- IF INR greater than 4.5 and no bleeding, oral vitamin K with INR monitoring
- IF minor bleeding, oral vitamin K
- IF life threatening bleeding, 4-factor PCC, then FFP by rapid infusion + IV vitamin K
Presentation of brodifacoum/superwarfarin toxicity - 1) timeframe 2) sources of rodenticide
- Spontaneous bleeding following toxic ingestion of rodenticide (in cereal bait, pellets, loose grain, paste)
- usually 24h delay until bleeding starts
- lasts for months (much longer half life)
Management of supratherapeutic INR
- Given INR 4.5-10 and no evidence bleeding, no indication for vitamin k (per American Society of Hematology guidelines)
- Given INR >10 and patient has no evidence of bleeding, recommend vitamin K 2.5 mg or 5 mg PO (per American Society of Hematology guidelines)
- Given bleeding OR urgent surgery/procedure needed, recommend
Vitamin K IV 10 mg once, slow infusion
4 Factor-prothrombin complex concentrate (PCC or Kcentra)
Management of low or intermediate risk MDS
- essentially observation until they become transfusion dependent
