Lecture 7 - Platelet Disorders Flashcards
Describe platelet hematopoiesis
Myeloid stem cells —> megakaryocyte
Megakaryocytes splinter into 2-3k fragments
Fragments get enclosed in plasma membrane
Describe a platelet
Disc-shaped with many vesicles
No nucleus
How do platelets stem bleeding?
They form a platelet plug
Their granules contain blood clot promoting chemicals
- ADP
- Thromboxane A2
Life span of platelets?
5-9 days
What controls platelet formation?
Thrombopoietin
Produced in the liver and stimulates megakaryocytes
You see a platelet abnormality on CBC, now what?
Ask yourself if its quantitive or qualitative
Fancy medical word for platelet clumping?
How do i r/o this with a platelet abnormality?
Pseudothrombocytopenia
R/o by repeating plt ct in non-EDTA containing tube
- sodium citrate tube
Youve narrowed it down to a quantative problem, what are some things that can cause this?
Reduced survival
Reduced production
What causes reduced survival of plt?
- Immune thrombocytopenia
- HIT
- TTP
- HUS
- Hypersplenism
- key
HIT (heparin induced thrombocytopenia)
TTP (thrombotic thrombocytopenic purpura
HUS (hemolytic uremic syndrome
What will cause reduced production of plt?
- Bone marrow disorder
- infection
- drugs
When are you more likely to notice qualitative plt disorders?
When clinically significant bleeding occurs
- Von Willebrand’s disease
- acquired disorders (uremia, drugs, ETOH)
- congenital causes
What is immune thrombocytopenia?
Autoimmune condition - antibodies bind PLTs, results in accelerated PLT clearance
Primary vs secondary immune thrombocytopenia?
Primary: idiopathic thrombocytopic purpura (ITP)
- MC
Secondary: disease/drugs
- autoimmune (SLE)
- lymphoproliferative d/o (chronic lymphocytic leukemia)
- connective tissue d/o
- HIV/Hep C
- drugs
Acute vs chronic immune thrombocytopenia?
Acute < 6mo
Chronic > 6 mo
Which populations are prone to acute vs chronic ITP?
Acute - kids
Chronic - adults
- secondary is also more likely to be chronic
Clinical features of ITP?
- Mild mucosal bleeding
- sever bleeding (old and sick pts)
- splenomegaly (uncommon)
- low plts (<50,000) if sever isolated form
Bleeding location follows the platelet count. As it descends what order does bleeding occur?
Skin
Mucous membrane
Viscera
If a ITP pt has no cutaneous petachie they have a low likelihood of?
Intracranial hemorrhage
I.e. they have a less sever form of ITP
How is ITP diagnosed?
Diagnosis of exclusion
- R/O Hep B, C, HIV
CBC - isolated thrombocytopenia
HX - must lack drug, etoh, food and herbal causes
Bone marrow bx
How long after starting a new drug will the pt get sever thrombocytopenia and mucotaneous bleeding if it is drug induced?
W/in 7-14 days
Who needs a bone marrow bx?
Older pts - r/o myelodysplastic syndrome
Unexplained cytopenias
Fail initial therapy
Prior to splenectomy
What is the goal of treatment with ITP?
To reduce risk of clinically important bleeding
- not to normalize plt count
Treatment for ITP?
Corticorsteroids =/- IVIG or anti-D
- mainstay of tx <30,000
PLT transfusion as needed
Tx for refractory cases of ITP?
Monoclonial antibodies
- rituximab
Splenectomy
- for failed tx or high dose steroids
Eltrombopag/romiplostim
- TPO-R agonist to stimulate plt production
Tx for asymptomatic pts or pts with plt count > 30,000-40,000?
There is only a 15% chance of sever thrombyctopenia requiring tx
- serial PLT counts
- watch for bleeding
- counsel pts on s/s of bleeds
What is HIT?
heparin induced thrombocytopenia
Lifethreatening complication of heparin (LMWH or unfractionated heparin)
- 5-10 days post heparin
- not dose related (even hep-locks)
- seen in 5% of pts w heparin
Pathophysiology of HIT?
Body forms IgG antibodies to heparin-platelet factor 4 (PF4) complexes
- leads to prothrombotic state
- macrophages eat the platelets —> thrombocytopenia
Types of HIT?
Mild - type I
- can continue heparin
Severe - type II
- hypercoagulatable state lasts for months
Describe type I HIT
Not immune mediated
- no clinical consequence
- modest thrombocytopenia (100,000)
- begins 1-2 days after therapy
What causes type I HIT?
We’re not sure but we think:
Direct effect of heparin on platelet activation (causing a non-immune platelet aggregation)
Describe type II HIT
- 5-10 days after tx
- immune mediated ab against Heparin PF4
- enhanced thrombin formation
- paradoxical thrombosis
- thrombocytopenia
- risk of DVT/PE/thrombosis
- hypercoagluatable state lasts weeks-months
When to suspect HIT?
Any of the following w/in 5-10 days of heparin
- unexplained thrombocytopenia
- venous/arterial thrombosis from thrombocytopenia
- PLT count drops 50% or more
- necrotic skin lesions at inj site
How is HIT usually diagnosed?
Clinically
The lab can confirm but it is slow
- ELISA test
- Serotonin release assay
- heparin-induced platelet aggregation
What is the 4Ts score for HIT?
Objective measure to determine if thrombocytopenia is HIT or something else
- Thormbocytopenia
- Timing of platelet count fall
- Thrombosis/sequelae
- Thrombocytopenia (Other causes)
Tx for HIT?
STOP HEPARIN
Switch to
- agratroban
- bivalirudin
- fondaparinux
After 3 months or when plt count reaches 150,000 pt can have warfarin
HIT pts also cannot have?
Warfarin - may worsen hypercoagulability
Until their platelet count is >/= 150,000
Prognosis?
Usually can use heparin again 100 days later (IgG ab dont last)
- < 100 days recurrence is high
But since other meds are available its best to just give them the other drugs
What is TMA?
Thrombotic microangiopathy
Acute complex syndrome w
- VASCULAR ENDOTHELIAL INJURY leading to WIDESPREAD THROMBI FORMATION in the microvasculature
- TTP AND HUS
Primary feature of vascular endothelai injury, TTP, and HUS that are required to be present for a diagnosis of TMA to be made?
MAHA - microangiopathic hemolytic anemia
- shearing of RBC (schitocytes)
Thrombocytopenia
Therapy for TMA?
Plasma exchange - removal of pt plasma and replacement with donar plasma
Most cases of TTP (thrombotic thrombocytopenic purpura) involve?
Acquired inhibitor of von Willebrand factor-cleaving protease
- ADAMTS 13
What is ADAMTS 13?
ADAMTS 13 attaches to endothelial cells and cleaves large vWF multimers
What happens with ADAMTS 13 when you get TTP?
Idiopathic:
Autoantibodies form against ADAMTS 13 leading to large accumulation of large vWF multimers that cause plt aggregation and thrombosis
- can also be 2/2 drugs, chemo, cancer
TTP presentation: FAT RN
F: fever
A: microangiopathic hemolytic ANEMIA
T: thrombocytopenia
R: renal disease (AKI)
N: neurologic complications (altered/confused)
What is HUS?
Hemolytic uremic syndrome
Simultaneous occurence of
- Microangiopathic hemolytic anemia
- Thrombocytopenia
- Acute kidney injury
Common cause of kidney injury in kids?
Hemolytic uremic syndrome
Kids always exhibit the classic triad
HUS s/s?
Petechial rash
HTN
Renal failure
Preceded by Gastroenteritis
If your HUS is not preceded by 0157:H7 or STEC it is considered?
Atypical
Usually medication, autoimmune, or some other type of infection
Therapy for HUS?
Supportive
FAT RN is the classic pentatd for TTP and HUS the presence of ___ and ___ should increases your suspicions
MAHA (microangiopathic hemolytic anemia)
and
thrombyctopenia
What findings common with TTP?
Neurologic
- Scattered thrombi formation in brain and subsequent impaired blood flow and O2 delivery
What findings are more common in HUS?
Renal findings
- microvascular thrombus formation and hemoglobinuria from intravascular hemolysis causing renal failure
Labs for TTP and HUS?
- thrombocytopenia
- fragmented cells on PBS
- hemolytic labs
— H LDH
— L haptoglobin
— H indirect bilirubin - NEG DAT (coombs)
- POS stool cx (HUS)
TTP tx?
Plasma exchange - removes antibodies to ADAMTS 13
- performed daily x 2 days
2nd line/refractory - immunosuppresion
- corticosteroids
- rituximab
- cyclosporine
quantitive platelet disorder causing reduced survival?
Hypersplenism - splenomegaly —> increased plt sequestration
quantitive platelet disorders causing decreased production?
Bone marrow disorder
Infection
Drugs
qualitative platelet disorder inherited?
vWF - coagulation problem
Platelet count is otherwise normal
Qualitative platelet disorder that is acquired?
Uremia
- renal failure from circulating toxins
Qualitative platelet disorder that are myeloproliferative?
Myleoproliferative disorders
- paradoxical bleeding risk - essential thrombocythemia and polycythemia vera
Normal numbers of platelets but they have abnormal function
Drugs that cause platelet disorders?
Aspirin - reduced aggregation
GP IIB/IIIA inhibitors
- abciximab
- eptifibantide
- tirofiban
Adenosine diphosphate inhibitors
- clopidogrel
- ticlodipine
You mama so FAT
When Dracula sucked her blood her got diabetes
