Bleeding disorders : solving q by lab results

IN PRESENCE OF BLEEDING TENDENCY

PATTERN 1

PT, APTT, Thrombin time, Fibrinogen concentration, Platelet count = All are normal

This scenario can occur mainly in following four conditions :-

[1] Platelet function defect

[2] Mild Von Willbrand disease

[3] Factor XIII deficiency

[4] Administration of Low Molecular Weight Heparin(LMWH)

IMPORTANT NOTE : Factor XIII deficiency leads to bleeding but show normal coagulation tests. It is associated with

Bleeding from stump of umbilical cord and habitual abortions Q
Impaired wound healing Q

 

PATTERN 2 : ISOLATED INCREASE IN PT

PT = Long

APTT, Thrombin time, Fibrinogen concentration, Platelet count = All are normal

This scenario can occur mainly in following  conditions :

[1] Factor VII deficiency (congenital/ liver disesase/ vitamin K deficiency)

[2] At start of oral anticoagulants.

 

PATTERN 3 : ISOLATED PROLONGED APTT

APTT = PROLONGED

PT, Thrombin time, Fibrinogen concentration, Platelet count = All are normal

This scenario can occur mainly in following  conditions :

[1] Deficiency in factor VIII , IX , XI , XII

[2] Cicculating anticoagulants eg Lupus anticoagulant

IMPORTANT NOTE : Factor XII deficiency doesnt cause clinicaly significant bleeding but leads to prolonged APTT.

 

PATTERN 4 : BOTH  PT and APTT  PROLONGED

Thrombin time, Fibrinogen concentration, Platelet count = are normal

This scenario can occur mainly in following  conditions :

[1] Vitamin K deficiency

[2] Oral anticoagulants

[3] Liver failure

[4] Factor II , V , X deficiency

 

PATTERN 5: PT and APTT and Thrombin time PROLONGED

Fibrinogen concentration = normal/abnormal

Platelet count =  normal

This scenario can occur mainly in following  conditions :

[1] In presence of unfractionated heparin ( TT usually very long)

[2] a/hypo/dys-fibrinogenemia.

 

Clinical Manifestations Typically Associated with Specific Hemostatic Disorders

Clinical Manifestations Hemostatic Disorders
Mucocutaneous bleeding Thrombocytopenias, platelet dysfunction, von Willebrand disease
Cephalhematomas in newborns, hemarthroses, hematuria, and intramuscular, intracerebral, and retroperitoneal hemorrhages Severe hemophilias A and B, severe deficiencies of factor VII, X, or XIII, severe type 3 von Willebrand disease, afibrinogenemia
Injury-related bleeding and mild spontaneous bleeding Mild and moderate hemophilias A and B, severe factor XI deficiency, moderate deficiencies of fibrinogen and factors II, V, VII, or X, combined factors V and VIII deficiency, 2-antiplasmin deficiency
 
Bleeding from stump of umbilical cord and habitual abortions Afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, factor XIII deficiency
Impaired wound healing Factor XIII deficiency
Facial purpura in newborns Glanzmann thrombasthenia, severe thrombocytopenia
Recurrent severe epistaxis and chronic iron deficiency anemia Hereditary hemorrhagic telangiectasias

 

 

 

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FETAL HEMATOPOIESIS

YOLK SAC

Erythropoiesis is established soon after implantation of the blastocyst, with primitive erythroid cells appearing in yolk sac blood islands by day 18 of gestation. Ie the first blood island appear in mesoderm at around 3 weeks of development.

How does yolk sac erythroblasts differ from their later definitive counterparts ?

[1] Primitive erythroblasts differentiate within the vascular network rather than in the extravascular space and remain nucleated as they circulate.

[2] Primitive erythroblasts are characterized by more rapid maturation, increased sensitivity to erythropoietin, and a shortened life span compared to fetal and adult erythroblasts.

[3] Yolk sac erythroblasts are extremely large red cells c/a megaloblasts

After 7 weeks gestation, hematopoietic progenitors are no longer detected in the yolk sac but yolk sac derived primitive erythroblasts continue to circulate until approximately 12 weeks of gestation.

SO HEMATOPOIESIS IN YOLK SAC = 3rd to 7th WEEK

Note that blood islands in yolk sac have HEMANGIOBLASTS arising from MESODERM. Hemangioblasts in centre of island form bood cells and are callled as HEMATOPOIETIC STEM CELLS and those in perifery differentiate into ANGIOBLASTS which form blood vessels.

LIVER :

Blood cells arising in blood islands of yolk sac is a transitory phenomena as the definitive hematopoietic cells arise from mesoderm surrounding aorta called as AORTA-GONAD-MESONEPHROS REGION (AGM Region). These cells will first colonise the liver which becomes major hematopoietic organ of liver  and later on these stem cells from liver will colonise the bone marrow.

BFU-E appear in the fetal liver as early as 5 weeks of gestation, and CFU-E are evident soon thereafter. The liver serves as the primary source of red cells from the 9th to the 24th weeks of gestation.

 

In contrast to the yolk sac, where hematopoiesis is restricted to erythroid and macrophage cells, hematopoiesis in the fetal liver also includes other myeloid as well as lymphoid lineages. So some “may be asked- NOT so important points” ( DNB oneliners)

[1] First RBC’S = 3rd week( yolk sac)

[2] Megakaryocytes are present in the liver by 6 weeks of gestation and Platelets are first evident in the circulation at 8–9 weeks gestation.

IMPORTANT NOTE POINT : The liver remains the primary site of erythropoietin transcription throughout fetal life as compared to kidney in adults.

BONE MARROW

Hematopoietic cells are first seen in the marrow of the 10- to 11- week embryo and they remain confined to the diaphyseal regions of long bones until 15 weeks gestation.The marrow becomes the major site of hematopoiesis after the 24th week of gestation.

 

NOTE : Lymphopoiesis is present in the lymph plexuses and the thymus beginning at 9 weeks gestation.

 

EMBRYONIC HEMOGLOBINs
[1] Hb PORTLAND = Zeta & gamma chains**
[2] Hb GOWER 1 = Zeta & epsilon chains **
[3] Hb GOWER 2 = Alpha & Epsilon chains**
FETAL Hb = HbF = Alpha & Gamma chains**

EMBRYONIC HEMOGLOBINS

Hb Gower 1 is the major hemoglobin in embryos less than 5 weeks of gestation****Q

Hb Gower 2 has been found in embryos with a gestational age 4-13 weeks.

Hb Portland is found in young embryos but persists in infants with homozygous  thalassemia.

At 10 -11 weeks fetal Hb becomes predominant Hb****Q

Adult Hb appears as early as 16- 20 weeks but synthesised in a nearly exclusive manner after 38 weeks.

Ref : [1] Langman’s medical embryology/10ed /pg 77

         [2] Williams Hematology, 8e , Chapter 6: Hematology of the Fetus and Newborn.


AIIMS MAY 2013 : SALIVARY GLAND TUMOR : HOT SPOT

Q ] Which of the follwing show ” HOT SPOT ” in technitium scan ……

[a] Adenolymphoma

[b] Mucoepidermoid carcinoma

[c] Acinic cell tumor

[d] Adenoid cystic carcinma

NOTE : SOME IMPORTANT POINTS ABOUT SALIVARY GLAND TUMORS

[1] Most common tumor of salivary gland = PLEOMORPHIC ADENOMA [AIIMS 1998 , AI 2002]

[2] Most common benign tumor of salivary gland =PLEOMORPHIC ADENOMA

[3] Most common benign tumor of parotid gland = PLEOMORPHIC ADENOMA

[4] Most common malignant tumor of parotid gland = MUCOEPIDERMOID CARCINOMA

[5] Most common benign tumor of parotid gland in children = HEMANGIOMA [2nd MC = PLEOMORPHIC ADENOMA]

[6] Most common malignant tumor of salivary gland in adult/ child/ overall = MUCOEPIDERMOID CARCINOMA

[7] Most common radiation induced neoplasm in salivary gland = MUCOEPIDERMOID CARCINOMA

[8] Most common malignant tumor of small salivay gland = ADENOID CYSTIC CARCINOMA ( CYLINDROMA )

[9] Only salivary gland tumor which show ” HOT SPOT ” on tecnitium scan = WARTHINS TUMOR = ADENOLYMPHOMA = PAPILLARY CYSTADENOMA LYMPHOMATOSUM

[10] SUPERFICIAL PAROTIDECTOMY = (is also known as) = PATEYS OPERATION

[11] Tumor which almost exclusively occurs in Parotid = ACINIC CELL ADENOCARCINOMA [AI 2006]

[12] Most common site of pleomorphic adenoma = PAROTID GLAND [AI 2006]

[13] Head & neck tumor in which perineural invasion is most commonly seen = ADENOID CYSTIC CARCINOMA [AI 2005]

[14] WARTHINS = ADENOLYMPHOMA [AIIMS 2003 , 2005]

[15] TREATMENT OF CHOICE FOR

[A] PLEOMORPHIC ADENOMA = SUPERFICIAL PAROTIDECTOMY( PATEYS OPERATION) [AIIMS 98, 2001, AI 97 ,PGI 99]

[B] WARTHINS = SUPERFICIAL PAROTIDECTOMY [ AIIMS 2001 , AI 98]

[C] ADENOID CYSTIC = RADICAL PAROTIDECTOMY

[D] MUCOEPIDERMOID LOW GRADE = SUPERFICIAL /TOTAL PAROTIDECTOMY

[E] MUCOEPIDERMOID HIGH GRADE = RADICAL PAROTIDECTOMY

[16] Most common site of minory salivary gland tumor = oral cavity = HARD PALATE

SO ANS = [A]

Ref: CSDT PAGE 293 / 11 ed

BLOOD TRANSFUSION

Q1] Permissible donor groups for FRESH FROZEN PLASMA transfusion if patients blood group is O ….
(a) O only
(b) O , A only
(c) O , A ,B only
(d) O , A , B , AB
(e) AB only

ANS = (d) O , A , B , AB

As plasma ( FFP ) will contain antibodies so in case of transfusion of FFP donor antibody and recipients antigen on RBC should be non reacting . If patients blood group is O then its RBC will contain neighter A nor B antigen so FFP having any type of ABO group antibody can be transfused.

See the table provided below for details

Image

Now if we consider this Q for PRBC transfusion with recipient being O group then ABO ANTIBODY in recipients plasma should be non reacting with ANTIGEN on donors RBC. So if recipient group is O then the recipients plasma will contain both Anti-A and Anti-B antibody so donor RBCS should be devoid of any ABO antigen to avoid hemolysis ie should be of O group only .

Q2] Permissible donor groups for PACKED RED CELL transfusion if patients blood group is O …

(a) O only
(b) O , A only
(c) O , A ,B only
(d) O , A , B , AB
(e) AB only

ANS = (a) O only

Q3] Which of the following BLOOD COMPONENT do not require ABO compatible product transfusion ie any ABO group product can be transfused….

(a) PLATELET CONCENTRATE

(b) PACKED RED CELLS

(c) FRESH FROZEN PLASMA

(d) CRYOPRECIPITATE

(e) BUFFY COAT

ANS = (a) and (d) See table provided below

Image

Q/A Hemolytic Anemia

Q1] Eculizumab( anti C5 antibody ) is used in treatment of…
[a] Hemolytic uremic syndrome
[b] Atypical Hemolytic uremic syndrome
[c] Paroxysmal nocturnal hemoglobinuria
[d] both a & c
[e] both b & c
[f] all

Ans : [e]
Eculizumab is FDA-approved for the treatment of

(1) atypical hemolytic uremic syndrome (aHUS) in adult and pediatric patients to inhibit complement-mediated thrombotic microangiopathy (TMA)

(2) treatment of paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis.

Eculizumab is not indicated for the treatment of patients with Shiga toxin E coli–related hemolytic uremic syndrome (STEC-HUS)

Q2] Which of the following statements is false about Donath- landsteiner antibodies…
[a] The Donath-Landsteiner antibody is responsible for complement-mediated hemolysis in paroxysmal cold hemoglobinuria
[B] It is an IgG antibody with P antigen specificity
[C] It is an IgM antibody with I antigen specificity
[D] It is a biphasic hemolysin which binds to RBC antigens at temperatures less than 37 degree C but does not cause hemolysis until the coated RBCs are heated to 37 degree C as they travel from the periphery to the core

Ans :
[C] It is an IgM antibody with I antigen specificity

Donath-Landsteiner antibody:

Paroxysmal Cold Hemoglobinuria is a rare form of Autoimmune Hemolytic Anemia occurring mostly in children, usually triggered by a viral infection, usually self-limited, and characterized by involvement of the so-called Donath-Landsteiner antibody. The Donath-Landsteiner antibody is responsible for complement-mediated hemolysis in paroxysmal cold hemoglobinuria.  It has anti-P specificity and binds to red cells only at a low temperature (optimally at 4°C), but when the temperature is shifted to 37°C, lysis of red cells takes place in the presence of complement.

[NOTE : Cold agglutinin disease ( different entity than PCH ) pertains to patients with chronic AHA in which the autoantibody directly agglutinates human RBCs at temperatures below body temperature ie binds and maximally active at a tempreature lower than body temp. Cold agglutinins typically are IgM with anti I specificity.

Q3] Paroxysmal nocturnal hemoglobinuria is due to a gene defect leading to impaired synthesis of …
[A] GPI
[B] CD55
[C] CD59
[D] All of above

Ans = [a]

Mutation in an X-linked gene, called PIG-A leads to  shortage of GPI in RBC membrane . GPI anchors CD55 and CD 59 to RBC membrane and these two prevent complement mediated lysis of RBCs so in a GPI deficient state RBC membrane lack CD 55 & CD59. So although hemolysis is due to deficiency of CD55 & CD 59 on RBC  membrane but their synthesis is not impaired.