Inherited and acquired vessel wall disorders Flashcards
Layers of vessel wall
Intima- innermost, covered by endothelium
Media-middle layer containing circularly arranged smooth muscle cells, collagen fibres
Adventitia - outermost , collagen and fibroblasts
Hereditary causes of Vascular bleeding
- Hereditary hemorrhagic telangectasia
- Ehler- Danlos syndrome
- Marfans syndrome
Metabolic and inflammatory causes of vascular bleeding
- Henoch schonlein syndrome
- Scurvy amyloid
- Steroid purpura
- Senile purpura
- Rickettsial diseases
- Polyclonal gammopathies
Method of inheritance of hereditary hemorrhagic telangectasia
Autosomal dominant
Pathophysiology of HHT
- Genetic defect that lead to mutations in endothelial protein endoglin
- This leads to dilated microvascular swellings known as telangiectasia which appear in childhood and become numerous in adulthood
- The microvascular swellings appear in the skin, internal organs and mucous membranes
Other signs present in HHT
- Pulmonary, hepatic, splenic, cerebral arteriovenous shunts
- Recurrent epistaxis
- Recurrent GI hemorrhage may cause chronic IDA
Treatment of HHT
Embolization- block where dilatations are Laser treatment estrogen tranexamic acid iron supplementation Thalidomide Lenalidomide Bevacizumab
What causes senile purpura
Atrophy of the supporting tissues of cutaneous blood vessels mainly in dorsal aspect of forearm and hand
What age group does senile purpura occur in
Older people
Microorganisms and infections can cause purpura by
Purpura from vascular damage by organism
DIC
Immune complex formation
Henoch schonlein syndrome is usually seen in
Children
Henoch schonlein syndrome usually follows
An acute upper respiratory tract infection
Henoch schonlein syndrome is mediated by this antibody
igA mediated vasculitis
Characteristics of Henoch Schonlein syndrome
- Purpuric rash
- Localised edema
- Itching
On which parts of the body are these characteristic properties of henoch scholeins dx found
Buttocks
Extensor surfaces of lower legs
Elbows
Other physical characteristics that may occur
Painful joint swelling
Haematuria
Abdominal pain
Occasionally kidney failuire
Henoch schonlein syndrome prognosis
Self limiting
Scurvy pathophysiology
Vitamin C is involved in formation of collagen. A deficiency in it will affect integrity of the vessel wall causing bruising , petechiae
Steroid purpura pathophysiology
Associated with long term steroid therapy usually in people with autoimmune diseases or cusions syndrome leading to a defect in vascular supporting tissues
Antifibrinolytic drugs that can be used in vascular disorders and thrombocytopenia
Tranexamic acid
Aminocaproic acid
Classification of platelet disorderd
- Quantitative - Has to do with number of platelets
2. Qualitative - Inherited and acquired disorders
Hereditary functional platelet disorders
Glanzmanns thrombastenia
Bernard soulier syndrome
Storage pool disease
Type of inheritance in glanzmanns thrombastenia
Autosomal recessive
Characteristics of glanzmanns thrombastenia
Prolonged bleeding time test
Platelets fail to aggregate with ADP , collagen, adrenaline, thrombin
Deficiency of platelet membrane GP2b-3a
Peripheral blood smear in Bernard soulier syndrome shows
Giant platelets, as big as RBC
Pathophysiology of glanzmanns thrombastenia
Problem with platelet aggregation due to defect in GP2b-3a
Method of inheritance in bernard soulier syndrome
Autosomal recessive mode of inheritance
Pathophysiology of Bernard soulier syndrome
Deficiency of platelet membrane GP1b causing deficient binding with vWf
Method of inheritance of atorage pool disease
Autosomal dominant inheritance
Pathophysiology of storage pool disease
Platelet granules are reduced in number and content
Abnormal formation of granules in megakaryocytes
Characteristics of storage pool diseases
- Mild bleeding in women
- Decreased platelet aggregation due to low secretion of ADP
- associated sometimes with oculocutaneous albinism
Bleeding in skin and mucous membrane is characteristic of this bleeding disorder
Platelet disorder
Bleeding into deep soft tissues like joints and muscles denotes
Coagulation factor disorders or secondary hemostasis disorders
Prescence of petechiae shows this bleeding disorder
platelet disorder
No petechiae shows that this bleeding disorder is absent
Coagulation factor disorder
Ecchymoses in platelet disorders are
small
superficial
Ecchymoses in coagu;ation factor disorders are
Large and deep
Muscle bleeding in platelet disorders are
Very rare
Hemarthrosis in coagulation factor disorders are
common
Bleeding after cuts and scratches is seen in
Platelet disorders only
Bleeding after surgery or trauma in platelet disorders is
Extremely mild, immediate
Bleeding after surgery or trauma when you have coagulation factor disorders coagulation
Are delayed for 1-2 days and often severe
Diagnostic approach to patient with mucocutaneous bleeding
- full blood count
2. Examination of peripheral blood smear
If examination of peripheral smear yielded low platelet count with large platelets the following conditions come to mind
ITP
Bernard-soulier
If peripheral smear exam shows low platelet count with normal sized platelets
Aplastic anemia
Amegakaryocytic thrombocytopenia
Leukemia
If peripheral smear shows Normal platelet counts with isolated platelets
Glanzmanns Thrombastenia
If peripheral smear shows normal platelets in clumps
von willebrands disease
platelet function disorders
Immune thrombocytopenic purpura
A situation where body produces autoantibodies against certain antigens on the platelets leading to destruction and low platelet counts
Most common immune destructive thrombocytopenia in adults and children
ITP
In children ITP is
Acute
resolves on its own
follows a viral infection
Affects both gender in equal proportions
In adults ITP is
Chronic
Usually diagnosed incidentally
More expressed in females
Diagnostic criteria for ITP
Thrombocytopenia with normal blood counts
No clinically apparent diseases that can cause thrombocytopenia
Pathogenesis of PLT
Increased platelet destruction along with inhibition of megakaryocyte platelet production
Clinical manifestations of ITP
Patient variability Severe Bleeding - easy bruising Mucocutaneous bleeding Uncommon intracranial hemorrhage Compared to vasculitic purpura is asymptomatic and not palpable
Initial treatment of ITP
> 50,000 - no treatment
20-50,000 - if no bleeding nothing; if there is bleeding give steroids and IVIG
<20,000 - If not bleeding give steroids
If bleeding give IVIG
Treatment of ITP
Steroids Splenectomy Intravenous immunoglobulin (IVIG) Rituximab Thrombopoiesis stimulating agents Recombinant FV11a
2nd line treatments for ITP
Recombinant FV11a
Splenectomy
Thrombopoiesis stimulating agents
Evamples of platelet stimulating agents
Romiplostin
Eltrombopag
Why are platelet transfusions not a mainstay form of treatment
It leads to further activation of antibodies which cause further destruction of platelets
