Hematology Flashcards
What is the treatment of Proximal DVT and PE?
Non cancer-associated (DOAC first line, if no contraindications)
– Provoked
* Tx for 3 months (up to 6 months)
– Unprovoked or chronic risk factor
* Tx for 3 - 6 months then assess bleeding risk; continue indefinitely with regular
reassessment of risk:benefit
Cancer-associated (LMWH or DOAC if no contraindications)
– Low/mod bleeding risk: indefinite therapy (1B) while active cancer
(+6 months in remission)
– Anticoagulation: DOAC or LMWH
* If using up front DOAC: must use apixaban or rivaroxaban, edoxaban requires 5d therapeutic
LMWH first
LMWH preferred where bleeding risk is high: high risk GI lesions (e.g. angiodysplasia,
varices), unresected intraluminal GI/GU cancer, high risk intracranial lesion (glioma, RCC,
melanoma), Child-Pugh class B/C, platelet < 50, recent bleed; DOAC Drug Interactions
What are contraindications to DOACS in VTE?
CAUTION IN:
1. Intraluminal GI malignancy not resected, GU (renal/bladder/prostate), ?intracranial malignancy
2. Renal: CrCl < 30 (apix <25; up to <15 but limited data), or dialysis
3. High clot burden: extensive/sub-massive PE, post-thrombolysis, iliofemoral DVT
4. Bariatric surgery: LMWH for first 4 wks–3 months | other malabsorption syndromes = consider LMWH
5. Drug-drug interactions: (eg) amiodarone increases levels of all DOACs [see Thrombosis Canada DDI guide]
2021 UPDATE: Rivaroxaban or Apixaban appropriate for any BMI/weight (except post bariatric sx.)
CONTRAINDICATION IN:
1. Liver failure: Child Pugh B and C
2. Anti-phospholipid antibody syndrome: arterial thrombosis, triple positive, small vessel thrombosis (livedo
reticularis, nephropathy)
3. Pregnancy AND Breastfeeding
4. Drug-drug interactions
(e.g. doxorubicin, cyclosporine, carbamazepine, phenytoin, azoles, protease inhibitors – bleeding risk): apix/riva CYP3A4/P-gp; dabi/edox P-gp)
5. Platelets < 50
DOAC Extension Studies (non-cancer associated)
In unprovoked VTE with low-med bleed risk > 6 mos of full dose treatment, consider lower dose-DOAC.
AMPLIFY – EXT (NEJM 2013)
N= 2482
Apix 5mg BID vs. 2.5 mg BID vs. placebo
Duration 12 mos
EINSTEIN CHOICE (NEJM 2017)
N = 3365
Riva 20mg daily vs. 10mg daily vs. ASA
81mg daily
Duration 12 mos
Caution in:
– Morbid obesity (Wt >120kg)
– Symptomatic pulmonary hypertension
– Index VTE event required thrombolytics
– Active cancer
– Thrombophilia
– Cost – low dose not always covered by drug plans for this indication
When to Use Warfarin for DVT?
“Be CALM”
Breastfeeding
CKD
Antiphospholipid Ab Syndrome
LV Thrombus (+ “Likes warfarin” – pt on warfarin stable for years)
– LV Thrombus (NB observational and 1 small RCT suggests DOAC
may be non inferior to VKA)
Mechanical Valve
– Mechanical valves [INR 2.5-3.5 – mitral, INR 2-3 - aortic]
What is the role of Thrombolysis in VTE?
DVT
- limb-threatening DVT (phlegmasia cerulea dolens)
- ASH: selected younger patients with iliofemoral DVT at high risk of Post thrombotic syndrome
(and low risk for bleeding)
PE
- hemodynamic instability (sBP <90 for over 15 mins) with no high bleeding risk (Gr 2B)
- IV thrombolysis with tPA (not catheter directed)
Bottom line:
Only thrombolyse PEs with hemodynamic instability, not for RV strain or ↑ trop
When do you use IVC filters?
IVC filter only if acute prox DVT (or PE*) & CI to A/C (grade 1B)
What are some complications of IVC filters?
Complications of IVC filters:
* Filter placement – bleeding, infection, malposition of filter, guidewire entrapment
* Post-procedure – DVT, hematoma, AV fistula
* Long-term – filter erosion/migration/embolization, chronic/recurrent VTE
– Filters may decrease risk of PE but increase risk of DVT and have no effect on mortality
When to treat distal DVT?
Severe symptoms, multiple deep veins involved, active cancer, ≥5 cm long, close to popliteal vein, irreversible risk factor, +D-dimer, or progression on repeat U/S
-consider full dose anticoagulation
(treat as proximal DVT)
- If high bleeding risk or no indication to treat monitor with serial U/S
When to treat subsegmental PEs?
Controversial
- Consider treatment if: active cancer/other
thrombotic risk, symptomatic, high D-dimer
When to treat superficial Vien thrombosis?
Superficial Vein Thrombosis:
- ≤3 cm from saphenofemoral junction à full
dose anticoagulation x 3 months
- > 3cm from SFJ and ≥5 cm long à
prophylactic anticoagulation x 45d
(fondaparinux 2.5 mg sc daily or rivaroxaban
10 mg po daily) - > 3cm from SFJ + <5cm long à NSAIDs and
monitor with serial U/S. ** Exceptions:
prophylactic anticoagulation in pregnancy,
cancer, surgery, trauma, prior hx of
SVT/DVT
3 Key points regarding COVID and Thrombosis
Non-hospitalized patients: no routine anticoagulation
– Including patients being discharged home post COVID19 admission = d/c anticoagulants
- Hospitalized non-critically ill: therapeutic intensity anticoagulation (heparin or LMWH
Suggested over prophylactic intensity based on evidence) - Critically ill: prophylactic intensity anticoagulation over intermediate/therapeutic dose
What is the treatment for Vaccine Induced Immune Thrombotic
Thrombocytopenia (VITT)?
No heparin
* Avoid platelet transfusions (unless life-threatening bleeding)
* 1st line anticoagulation: anti-Xa DOACs
* Send HIT ELISA before IVIG
* IVIG 1g/kg actual body weight daily x 2 days
* Consult hematology
Reversal Agents for Anticoagulants
Warfarin
Non-bleeding:
* INR >9: hold warfarin + VitK 2.5-5 mg po
* INR 4.5-9: hold warfarin + decrease dose
Non life-threatening bleed:
* Vit K + supportive
Life threatening bleed/imminent
procedure:
* IV Vit K + prothrombin complex (PCC)
– PCC dosing per INR: INR 1.5-3: PCC 1000U;
INR 3-5: PCC 2000U; INR> 5: PCC 3000U
LMWH
Life threatening bleed:
* Protamine 25-50 mg
Heparin
- Protamine dose based on last admin
DOACs
Non life-threatening: supportive
Life-threatening bleed: supportive +
* Dabigatran:
* Idarucizumab (Praxbind) 2.5g x 2 doses;
consider dialysis (~65% removal in 4 h)
- Apixaban/Rivaroxaban/Edoxaban:
- 4 factor PCC (e.g. Octaplex, Beriplex);
2000U (can be repeated)
Differences between Primary vs secondary hemostasis?
Clinical Presentation - Primary Hemostasis
* Mucocutaneous bleeding
* Easy bruising
* Heavy menstrual bleeding
* Petichiae (low plts)
Labs: +/- ↓ plts, often coags normal
DDx
1. VWF Deficiency
Von Willibrand Disease (VWD)
2. Plt Disorder
↓Quantity -e.g. ITP
↓ Quality -e.g. ASA, uremia, congenital
Secondary Hemostasis
Clinical Presentation:
* Hemarthrosis
* Intramuscular bleeding
* Retroperitoneal bleeding
Labs: abnormal coag. tests
DDx [see slides specific to INR/PTT]
1. Coagulation factor deficiency
* Hemophilia A (Factor VIII)
* Hemophilia B (Factor IX)
* Warfarin (II, VII, IX, X)
2. Coagulation factor inhibitor
* Idiopathic/various diseases
* Medications: DOACs
What is the Approach to Isolated Elevated PT or aPTT ?
Elevated PT (INR)
* Step 1 - rule out pre-analytical error,
medication contamination etc.
* Step 2 = 50:50 mixing study:
A. PT corrects = factor deficiency
* If FVII low (<50%) à factor
deficiency confirmed
* DDx:
congenital/acquired
FVII deficiency, vit K
def., liver disease
B. PT does NOT correct = inhibitor
present
- Check FVII level
- If VII low, check
inhibitor level
Elevated aPTT
* Step 1 - rule out pre-analytical error, medication
contamination Step 2 - 50:50 mixing study 50:50 mixing
study interpretation:
A. aPTT corrects = factor deficiency
– Measure factors VIII, IX, XI, XII (intrinsic
pathway)- 8.9.11.12
* Etiologies: Acquired vs. congenital factor
deficiency vs.VWD
* Confirm by measuring relevant factor
levels (<50% is low)
B. aPTT does NOT correct = inhibitor present
– Lupus anticoagulant (LA) testing
» LA positive - r/o APLA (see rheum lecture)
* Presence of LA is a risk for THROMBOSIS
not bleeding!
» LA negative - factor inhibitor
Measure factors VIII, IX, XI then inhibitor
What is the presentation of VWD?
- Most common bleeding disorder
- ↓quantity or quality of Von Willebrand Factor
- VWF: 1o - plt adhesion and 2o – protects FVIII
Presentation: mucocutaneous bleeding, heavy menstrual bleeding, easy bruising
How do you diagnose VWD?
Diagnosis:
-VWF Ag (quantity), VWF:Ristocetin Cofactor or VWF:GP1bR (VWF activity), FVIII level
* aPTT can be NORMAL in VWD, NOT a good screening test
* VWF :↑ stress, estrogens, pregnancy ; ↓levels in blood group O
Diagnosis (Continued)
* Type 1: Quantitative deficiency (↓VWF:Ag [<30%] = ↓VWF Rco [<30%] ie. concordant; ratio>0.7)
– VWF < 30% or VWF 30-50% + abnormal bleeding = diagnostic
* Type 2: Qualitative deficiency of VWD (↓/↔ VWF Ag [<30-200%], ↓↓VWF:Rco [<30%] ie.
discordant; ratio<0.7)
- Multiple subtypes
* Type 3: No VWF produced (↓VWF:Ag [<5%] = ↓VWF:Rco [<5%]; ↓↓ factor VIII) - Behaves like Hemophilia A
What is the treatment of of VWD?
Treatment:
* Acute Bleeding/Peri-Op: TXA for all
– DDAVP: boosts vWF level (can work for Type 1; not in type 2B/2N or 3)
– Blood products:
* plasma derived concentrates of vWF and FVIII (e.g. Humate P)
What is the work up for ITP?
Definition: Plt < 100 in the absence of other causes
* Presentation: mucosal bleeding, petichiae, wet
purpura
* Workup:
– CBC, blood film, HCV, HIV serology
– Bone marrow biopsy not necessary
– H. pylori – test if eradication therapy would be
used
Treatment for ITP?
Treatment
1) NOT BLEEDING/MILD MUCOCUTANEOUS BLEEDING &
PLT >30
* Watch and wait
2) NOT BLEEDING & PLT < 30
* 1st line: Pred 0.5-2mg/kg or Dex 40 mg X 4d, IVIG
(if C/I to pred; caution: hemolysis), anti-D (RhD+; caution: hemolysis)
– FLIGHT: MMF + steroids
* 2nd line: splenectomy, rituximab, TPO-R agonists
3) ACTIVE BLEEDING
* Steroids + Tranexamic Acid +/- IVIG
* Life threatening: Plt transfusion +/- splenectomy
Myeloid vs. lymphoid disorders
– Myeloid = RBCs, platelets, monocytes, granulocytes
– Lymphoid = B-cells, T-cells
Myeloid Disorders
- Acute Myeloid Leukemia (AML)
– too many immature myeloid cells (i.e. myeloid blasts) - Myeloproliferative Neoplasms (MPNs)
– too many mature myeloid cells
* too many RBCs = Polycythemia vera (PV)
* too many platelets = Essential thrombocytosis (ET)
* too many granulocytes = Chronic Myelogenous Leukemia (CML) - Chronic Myelomonocytic Leukemia (CMML)
– features of BOTH MPN and MDS
* too many monocytes
* myeloid cells are dysplastic - Myelodysplastic Syndrome (MDS)
– not enough myeloid cells (cytopenias) à bone marrow failure
* ineffective hematopoiesis
* myeloid cells are dysplastic
Lymphoid Disorders
- Acute lymphocytic leukemia (ALL)
– too many immature lymphoid cells (i.e. lymphoid blasts) - Lymphoproliferative disorders (LPDs)
– too many mature lymphoid cells
* CLL: burden of disease is in the peripheral blood
* Lymphoma: burden of disease is in lymph node
* Waldenstrom Macroglobulinemia /Lymphoplasmacytic lymphoma - Plasma cell dyscrasias
– Too many plasma cells → overproduction of a single antibody / light chain
* MGUS → smoldering myeloma → multiple myeloma
* Primary amyloidosis
Acute Leukemia (too many immature cells)
Etiology:
* de novo vs. 2o (prior chemo, transformed
MDS,/MPN, congenital d/o (e.g. Fanconi
Anemia, Down Syndrome), benzene)
Presentation:
1. BM failure (loss of normal hematopoiesis)
– Cytopenias:
* Anemia (fatigue), thrombocytopenia
(bleeding), neutropenia (infection)
- Systemic symptoms (due to blasts)
– Leukostasis, DIC, tumor lysis syndrome
– Organ dysfunction
* Skin - rash
* Mucosa - gum hypertrophy
* CNS - Neuro symptoms
Diagnosis:
* ≥ 20% blasts in peripheral blood or marrow*
* WHO classification relies on genetic mutations
* Distinguishing AML from ALL:
– Based on BM biopsy, flow cytometry,
cytogenetics, molecular
– Auer rods only in myeloid neoplasms à
Auer rods never normal
Blast cells + Auer rods + DIC think ?
APL=Acute promyelocytic leukemia
- Subtype of AML
- T(15;17) PML-RARA
- Most curable AML type
- ↑early mortality from DIC:
- Intracranial hemorrhage
- Blood clots
- Urgent treatment: ATRA
all-trans retinoic acid (tretinoin)
Acute Leukemia Associated Emergencies-
Tumor Lysis Syndrome definition and Treatment
- Tumor lysis syndrome
* ↑K, PO4, uric acid (UA), ↓ Ca
* AKI, seizures, arrhythmias
Treatment:
1. Manage hyper-K, correct ext. lytes
2. IVF (target UO 80-100 mL/m2/h)
AND EITHER:
3. Allopurinol
OR
4. Rasburicase if: AKI, ↑↑ uric acid
(>535 umol/L), no response to allopurinol
(NOT in G6PD def)
Acute Leukemia Associated Emergencies-
Leukostasis definition and treatment
- Leukostasis (AML>ALL>CML»CLL):
* Rigid sticky blasts ↓flow → organ dysfunction
* Can affect any/all organ systems
* Lungs (dyspnea/hypoxia)
* CNS (confusion/visual changes)
* In AML if WBC >50-100
* At higher WBC in CML/ALL, rare in CLL
Treatment:
1. IVF
2. Cytoreduction (e.g hydroxyurea, leukapheresis,
induction chemo)
3. TLS prophylaxis
4. Avoid transfusion
