Medical - Heme - Onc - Diabetes Flashcards
In a pregnant patient with thrombocytopenia, what is your differential diagnosis?
Gestational thrombocytopenia Pseudothrombocytopenia (Platelet clumping) ITP - antiphospholipid syndrome - lupus TTP / HUS / DIC Preeclampsia / HELLP syndrome HIV / Hep C / CMV Meds: Heparin
In a pregnant patient with thrombocytopenia, what is your workup?
H&P (heavy menses, easy bruising/bleeding, medications, petechiae)
vitals (BP assessment)
CBC
Peripheral smear (pseudothrombocytopenia/clumping)
What is gestational thrombocytopenia? What causes it?
Thrombocytopenia that can occur in pregnancy due to hemodilution and enhanced clearance
How can gestational thrombocytopenia be distinguished from ITP?
ITP:
Also seen out of pregnancy
Can be symptomatic
Associated with neonatal thrombocytopenia
Gestational:
Not outside of pregnancy
Asymptomatic
No neonatal thrombocytopenia
Platelet count usually above 75k and return to normal postpartum
Management of suspected Gestational thrombocytopenia?
CBC follow up
Postnatal CBC to assess resolution
What is ITP?
Immune thrombocytopenic purpura, an autoimmune disorder where antibodies cause destruction of platelets
What causes ITP?
Primary: Autoimmune destruction of platelets
Secondary: HIV, HCV, SLE or Leukemia
Drug induced: Heparin, NSAIDs monoclonal antibodies
How is ITP diagnosed?
Base on history, labs and physical exam findings, mostly a diagnosis of exclusion
What are potential complications associated with ITP in pregnancy?
“Bleeding
Fetal/neonatal thrombocytopenia”
If a patient presented with suspected ITP at 35 weeks with a platelet count of 40,000, How would you counsel her?
Counsel that there is no test to predict course of platelets for her or fetus
Try to minimize bleeding
If she has an indication for a cesarean, we can discuss increasing platelets with steroids
Avoid NSAIDs
If a patient presented with suspected ITP at 35 weeks with a platelet count of 40,000, How would you manage her?
Multidisciplinary approach (Anesthesia, hematology, neonatology)
What are treatment options for ITP in a pregnant patient?
Steroids (Prednisone 0.5mg/kg daily, see response in 2 weeks)
IVIG (see response in 3 days)
Platelet transfusion (3X dose + intravenous high-dose corticosteroids or IVIG)
Splenectomy (avoid in pregnancy)
Rhogam (decreases platelet destruction)
Considerations for labor and delivery and neonatal care in ITP?
“Avoid scalp electrodes / operative vaginal delivery
Neonatal platelet count after delivery and at 2-5d of life
Avoid IM injections / circumcisions till platelet count returns”
When is treatment of ITP warranted?
“Symptomatic bleeding
Platelet count below 30,000
Expected surgery and platelet count <50,000
Neuraxial anesthesia desired and platelet count <70,000”
What are the fetal risks if the mother has ITP?
Fetal thrombocytopenia with hemorrhage (risk is less than 1%).
Below what platelet treshold is neuraxial anesthesia no longer allowed?
What is the goal platelet count before cesarean section?
Neruaxial anesthesia: 70,000
C/s: 50,000
What are the risks of neuraxial anesthesia in a thrombocytopenic patient?
Epidural hematoma
How do you counsel a patient with HELLP syndrome regarding her risks during cesarean section?
Risks of bleeding, DIC, seizures
How do you monitor / counsel about platelets counts after delivery in HELLP syndrome?
“Nadir is about 48 hours postpartum
Most platelet counts are above 100,000/L within a week”
“G1P0101 with a history of a prior 32 week delivery.
She remembers going to hospital with abdominal pain, n/v and confusion.
SHe was told she had mild fever and AST/ALT of 700/800, Bilirubin of 5, WBC 17k, Platelets of 22k and creatinine 2.2.
What is your D/Dx for what prompted this delivery?”
“Acute fatty liver of pregnancy
TTP / HUS
HELLP syndrome
Lupus with flare”
What would help you make a more definitive diagnosis of acute fatty liver of pregnancy?
“Very high LFTs
High Ammonia
Hypoglycemia
Prolonged PT/PTT
Decreased Antithrombin level
Decreased fibrinogen”
Etiology of AFLP?
“It can be due to Long Chain 3hydroxyacyl CoA Dehydrogenase (LCHAD) deficiency
But other enzyme deficiencies have also been demonstrated (more rare)”
If the diagnosis was Acute fatty liver of pregnancy, how do you counsel her regarding a future pregnancy?
Higher risk of recurrence in another pregnancy, but unclear how high
~25%
Follow up in future pregnancies when AFLP occurred prior?
Baseline labs, and increased monitoring of labs starting 1 month prior to gestational age of prior diagnosis.
“Pregnant patient in the ICU with a platelet count of 5, high fever and was not arousable.
What is your differential diagnosis?”
“Thrombotic thrombocytopenic purpura
HUS
DIC
HELLP
AFLP”
What findings should make you suspect TTP?
“Microangiopathic hemolytic anemia (MAHA)
Thrombocytopenia
Fever
Acute Kidney Injury
Severe neurologic findings”
What lab test is a hallmark of TTP?
Reduced ADAMTS13 activity (<10%)
What is the treatment for TTP?
“Plasmapheresis in consultation with Hematology / Critical care
Steroids
Avoid platelet transfusion as can precipitate disease”
If you suspect a hemophilia, what tests would you send?
Factor 8
Factor 9
VWF antigen
ristocetin cofactor activity level
What are the risks of VWD in pregnancy?
Increased risk of bleeding
Risk of fetus having VWD
How do you follow patients with VWD in pregnancy?
Meds to avoid?
Labs?
Hematology for comanagement
Genetic counsultation
Anesthesia consult
Avoid antiplatelet drugs and IM injections
Labs q trimester:
-Factor 8
-Ristocetin cofactor activity
-VWF antigen
Goal VWF ristocetin cofactor activity level?
“50% for vaginal
100% for c/s”
How do you treat VWF in case of emergency or preoperativelly?
DDAVP intranasally or IV (elicits release of VWF from endothelial cells)
VWF precautions during labor and for newborn?
“No scalp electrodes
Avoid episiotomy
Avoid circumcision until VWD ruled out”
How is VWD inherited?
Autosomal Dominant
How are hemophilias inherited?
X linked recessive
Which patients should be screened for thrombophilia in pregnancy?
“Personal history of VTE (w/ or w/out risk factor and no prior testing)
1st degree relative with high risk thrombophilia”
When screening for thrombophilia what tests do you send?
“Prothrombin gene mutation - DNA analysis
Antithrombin 3 deficiency - Antithrombin activity
Protein S deficiency - Protein S Functional assay
Protein C deficiency - Protein C activity
Factor V Leiden - Activated protein C resistance -> DNA analysis”
What thrombophilia test results are not impacted by pregnancy?
All of the main ones are not impacted, only Protein S is
What are the most common thrombophilias?
1 Factor V leiden heterozygote (1-15%)
#2 Prothrombin gene mutation (2-5%)
What are the low risk thrombophilias?
“FVL heterozygote
PT gene mutation heterozygote
Protein C deficiency
Protein S deficiency”
What management do you offer for low risk thrombophilias without a prior VTE?
Antepartum vs. postpartum?
“Antepartum:
Surveillance without anticoagulation
Postpartum:
Surveillance or prophylactic anticoagulation (if additional risk factors such as obesity, c/s, or prolonged immobility)”
“What management do you offer for low risk thrombophilias with a family history (1st degree relative) of VTE?
Antepartum vs. postpartum?”
“Antepartum:
Surveillance without anticoagulation OR
Prophylactic dose anticoagulation
Postpartum:
Prophylactic dose anticoagulation OR
Intermediate dose anticoagulation”
“What management do you offer for low risk thrombophilias with a single episode of VTE - not receiving long term anticoagulation?
Antepartum vs. postpartum?”
“Antepartum and postpartum:
Prophylactic dose anticoagulation OR
Intermediate dose anticoagulation “
What are the high risk thrombophilias?
“FVL homozygote
PT gene mutation homozygote
FVL and PT combined heterozygote
Antithrombin 3 deficiency”
“What management do you offer for high risk thrombophilias without a prior VTE?
Antepartum vs. postpartum?”
“Antepartum and postpartum:
Prophylactic dose anticoagulation OR
Intermediate dose anticoagulation “
“What management do you offer for high risk thrombophilias with a personal history of a previous single VTE or a family history (1st degree relative) of VTE?
Antepartum vs. postpartum?”
“Antepartum and postpartum:
Prophylactic dose anticoagulation OR
Intermediate dose anticoagulation OR
Adjusted dose anticoagulation”
Which thrombophilias are candidates for adjusted dose (therapeutic dose) anticoagulation?
High risk with personal history
High risk with 1st degreefamily history
Any thrombophilia with 2 or more epsiodes of VTE
What are the risks and benefits of UFH use in pregnancy?
“Risks: unpredictable pharmacodynamics (dose-response), severe bleeding complications, and the risk of HIT
Benefits: prevention of VTE, short halflife / easy reversibility”
What are the risks and benefits of LMWH in pregnancy?
“Risks: severe bleeding complications
Benefits: once daily dosing prophylactically, lower risk of HIT”
Describe how you manage anticoagulation near-term in a patient on LMWH?
Switch from LMWH to UFH due to the easier reversibility / short halflife of UFH.
How long do you hold LMWH prior to IOL or C/S?
Prophylactic: 12 hours before IOL or C/S
Adjusted dose: 24 hours before IOL or C/S
How is FVL inherited?
Autosomal dominant
Is FVL a low-risk or high risk thrombophilila?
“Low risk if heterozygote
High risk if homozygote”
What is the risk of VTE in a patient with a low risk thrombophilia?
0.5-3%
As high as 6% in protein s deficiency
How is prothrombin gene mutation inherited?
Autosomal dominant
Is prothrombin gene mutation a low or high risk thrombophilia?
“Low risk if heterozygote
High risk if homozygote”
Anticoagulation offered ante and pp? LR No hx: LR fam hx: LR Pers hx: HR no hx: HR fam or pers hx: 2+ clots not on lt coag: 2+ clots on lt coag:
LR No hx: S SP
LR fam hx: SP PI
LR Pers hx: PI PI
HR no hx: PI PI
HR fam or pers hx: PIA PIA
2+ clots not on lt coag: IA IA
2+ clots on lt coag: A Lt coag
What is antiphospholipid antibody syndrome?
Autoimmune disorder defined by presence of clinical features and circulating antiphospholipid antibodies
How is antiphospholipid antibody syndrome diagnosed?
1 positive clinical criteria and 1+ positive lab criteria on 2 occasions 12 weeks apart.
What are the clinical criteria for the diagnosis of antiphospholipid antibody syndrome?
“1: Vascular thrombosis
2: Pregnancy morbidity:
(a) 1+ SAB after 10 weeks (unexplained, morphologically normal)
(b) 3+ SAB before 10 weeks (consecutive, unexplained, maternal hormonal/anatomic and parental chromosomal abnormalities ruled out)
(c) Pregnancy complicated with placental insufficiency, eclampsia/severe preeclampsia before 34 weeks”
What are the laboratory criteria for the diagnosis of antiphospholipid antibody syndrome?
(1) Lupus anticoagulant +
(2) Beta 2 glycoprotein IgM, IgG (titer greater than 99th percentile)
(3) Anticardiolipin antibody IgM, IgG (greater than 40 GPL or MPL, or greater than the 99th percentile)
How do you counsel a patient about the risks of antiphospholipid antibody syndrome?
thrombosis
preeclampsia
fetal growth restriction
fetal loss
autoimmune thrombocytopenia autoimmune hemolytic anemia
What are the rare complications of APS?
livedo reticular is cutaneous ulcers chorea gravidarum multiinfarct dementia transverse myelitis
How do you manage pregnancy in a patient with antiphospholipid antibody syndrome?
Hx of stillbirth, RPL: heparin and aspirin
Prior thrombotic event: heparin
No prior thrombotic event: surveillance or heparin
How do you manage anticoagulation postpartum for patients with antiphospholipid antibody syndrome?
“If no history of thrombosis: Postpartum heparin/aspirin x 6 weeks
If there is a history of thrombosis: Warfarin (lifelong)”
Long term risks of antiphospholipid syndrome?
Thrombosis, SLE
“42 yo G6P3023 at 11 weeks with history of stroke 2 years ago.
Meds: plavix, aspirin 81mg, Atorvastatin.
MTHFR homozygote
3 prior uncomplicated vaginal deliveries >10 years ago
What is your initial workup for this patient?”
“Targeted H&P specifically asking about residual symptoms, if the patient has ever been told to be on lifelong anticoagulation, is she followed by a neurologist fam hx of VTE
Inherited thormbophilias and APLS workup
Consider basic coags / cbc
+/-Imaging of the brain
Request old records”
“42 yo G6P3023 at 11 weeks with history of stroke 2 years ago.
Meds: plavix, aspirin 81mg, Atorvastatin.
MTHFR homozygote
3 prior uncomplicated vaginal deliveries >10 years ago
Labs: low protein C and S prior to pregnancy and not on anticoagulation
Negative for APLS
Records show 50% stenosis of internal carotid artery.
What is your plan of management for this patient in the antepartum period?”
“Neurology consultation (follow up for carotid scan)
Discontinue statins
Discontinue plavix
Start LMWH (talk to neuro about prophylactic vs. intermediate)
Continue ASA, add 1mg folic acid
Maternal Echo (PFO)
Counsel on low saturated fat diet
Growth / Antenatal testing “
What is alpha thalassemia?
Disorder of decreased alpha globin gene production due to gene microdeletions.
What does it mean to be a silent carrier for alpha thalassemia?
Microdeletion of 1 of 4 alpha globin genes
What is alpha thalassemia minor?
“Microdeletion of 2 of 4 alpha globin genes
Mild microcytic anemia”
What are the two forms of alpha thalassemia minor?
cis (both deletions on the same side), trans (both deletions on opposite sides)
What is Hemoglobin H disease?
“Microdeletion of 3 of 4 alpha globin genes.
HbH forms which is a β tetramer (4 x β chains)
Moderate microcytic anemia”