SMTP/transport failure twice in the last 2 weeks (Exchange 2013)

Twice in the last 2 weeks, my Exchange 2013 server SMTP/Transport services have crashed resulting in halt of all mail traffic, internal and external, both occasions requiring unplanned restarts.  After diving into the logs, I tend to believe that this is a larger-scale SMTP failure rather than an individual transport service going sideways.  A brief description follows:

Virtualized machine running Server 2012 and Exchange 2013
Exchange 2013 running as CAS and MBX server
Outgoing mail exits network directly through firewall
Incoming (external) mail is first screened by external-facing Spamassassin/Postgrey server, then relayed to Exchange via firewall

When the failure occurs, all mail-flow comes to a screeching halt, internal mail as well as incoming and outgoing external mail.
Restarting of Microsoft Exchange Frontend Transport, Microsoft Exchange Mailbox Transport Delivery, and Microsoft Exchange Mailbox Transport Submission services had no effect.  During last occurrence, the lattermost service failed to successfully stop during commanded restart. 

During failures, maillogs on external Spamfiltering server reflect inability to contact Exchange via SMTP (firewall incoming port 25 is port-forwarded to Exchange).
During failures, internal transport message tracking logs report inability to pass mail due to no contact on local port 2525, which from what i understand is the alternate SMTP port that mailbox transport uses when MBX and CAS roles are on the same server.

At this point, I don't know where else to look for the root cause of the failure.  Any suggestions for preventative measures or further sources to check for troubleshooting would be greatly appreciated.

Logfile excerpts below:

from spam filtering server:
Aug 19 13:46:16 spam postfix/smtp[27872]: connect to <firewall IP>[<firewall IP>]:25: Connection timed out
- pretty self-explanatory

from Exchange message tracking log
2013-08-19T20:18:43.920Z,fe80::355f:c11:7a17:2b35%12,BLUEDC,,,"MDB:ce47122a-1259-41c6-8007-e024d35cce8e, Mailbox:3cb300c0-8126-4ba0-a559-6085356fa4da, Event:4138182, MessageClass:IPM.Note, CreationTime:2013-08-19T19:58:37.202Z, ClientType:MOMT",,STOREDRIVER,SUBMITDEFER,,<b241fd62fc0741cd8cf19ee307274e09@<server FQDN>>,eee0545ff02f4c0ff00308d06b2f09d7,xxxxxxx@xxxxx.com;xxxxx@xxxxx.com;xxxxx@xxxxx.com,,,3,,,,xxxxx@xxxxx.com,,2013-08-19T19:58:37.202Z;LSRV=bluedc.sc.bps:TOTAL=1206|MTSSN=605|SMS=600|MTSSDMO=600|MTSS=600,Originating,,,,"S:ItemEntryId=00-00-00-00-9D-3B-0A-45-8E-EF-B3-40-8F-B4-F9-F6-51-5D-62-6C-07-00-81-2E-8F-B9-91-62-10-49-AD-D1-28-F0-28-CB-FC-3A-00-00-00-00-00-0D-00-00-81-2E-8F-B9-91-62-10-49-AD-D1-28-F0-28-CB-FC-3A-00-00-44-65-81-F2-00-00;S:DiagnosticInfo=Error: RetrySmtp, Diagnostic Information: Stage:CommitMailItem, SmtpResponse:451 4.4.0 Error encountered while communicating with primary target IP address: ""421 4.4.2 Connection dropped due to TimedOut."" Attempted failover to alternate host, but that did not succeed. Either there are no alternate hosts, or delivery failed to all alternate hosts. The last endpoint attempted was 192.168.254.22:2525"

August 20th, 2013 8:29pm

Hello,

You will need to check the application log to know the specific event ID when the service crashed.

Regards,

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August 24th, 2013 11:16am

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